基于中国汉族人群的精神分裂症候选基因的关联研究分析
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摘要
精神分裂症(schizophrenia)是最严重最常见的精神疾病之一,在全世界各个人群中普遍存在,发病率在1%左右。主要表现为特征性的感知、思维、情感和行为的障碍以及精神活动与环境的不协调。同胞对分析、家系分析以及寄生子的研究一致表明,遗传因素在发病机制中起了重要的作用。目前对于精神分裂症的发生被认为是在环境因素影响下,多个中至微效基因协同作用的结果。本论文从基因组水平上出发,研究了KIF2和PDLIM5在中国汉族人群中与精神分裂症的相关性。
KIF2是动力蛋白Kinesin家族的一员,在哺乳动物的神经元生长过程中承担重要的转运膜复合体和蛋白复合体的作用,并且通过在生长锥的边缘解聚微管调节微管动力。Homma等报道Kif2a基因敲除的小鼠在海马体的CA1和CA3区域出现了不正常的松散排列;而且在海马神经元的体外培养实验中,Kif2a-/-的海马神经元细胞在缺失了KIF2蛋白的抑制侧枝生长后较野生型神经元细胞长出很多侧枝。因此,KIF2很有可能是精神分裂症的易感基因之一,具有功能候选的特性。小鼠Kif2基因的同源基因在人类基因组的5q12.1。为了检测KIF2基因与精神分裂症发病的相关性,我们根据NCBI数据库中已有的KIF2基因的信息,选择了四个常见高频率单核苷酸多态性(Single Nucleotide Polymorphism,SNP)位点,并用软件设计了PCR引物,在中国汉族人群280个核心家系样本中,用等位基因实时PCR技术试验获得了样本所选四个位点的基因型,进而根据基因型数据和家系样本的结构,用ETDT、2LD、Hapview和FBAT软件分析了KIF2基因和精神分裂症的相关性。所选四个常见SNPs位点的关联分析中没有得到任何显著性结果。然而,本研究发现一个2-SNP的核心区域(rs2289883/rs464058,G/A)单倍型分析结果与精神分裂症密切相关;此外研究发现一个拥有23.4%的频率的常见4-SNP的单倍型(T/G/A/G)与精神分裂症相关(P=0.00795)。实验结果支持了KIF2基因是精神分裂症的易感基因之一的假设。
PDLIM5是一个LIM结构域的蛋白,在细胞骨架的组织,细胞系的分化,器官发育和肿瘤形成中都有重要作用。这个蛋白同时也是Enigma蛋白家族中的一员,具有典型的由N端PDZ结构域和C端的1-3个LIM结构域构成的典型特征。PDLIM5蛋白在大脑的许多区域都有表达,包括海马体,皮层,丘脑,丘脑下部,杏仁体和小脑。在海马的神经元上,PDLIM5蛋白分布在突触后,是阿尔茨海默症发病期过渡表达蛋白AD7c-NTP的同源蛋白。Iwamoto等研究者发现在精神分裂症和双向情感障碍的患者的淋巴细胞系中,PDLIM5的mRNAs的量较正常人的量偏低,但是在精神分裂症、双向情感障碍以及抑郁症的患者的脑中,PDLIM5的mRNAs的量较正常人偏高。Kato等研究者报道了PDLIM5 mRNA在精神分裂症和双向情感障碍的患者脑中表达上调。从基因组研究的角度上,PDLIM5定位于人类基因组的4q22.3的位置,这一区域已经被多个连锁研究证明是精神分裂症的阳性区域。以上蛋白功能方面和连锁方面的证据提示,PDLIM5可能是精神分裂症的易感基因之一。因此,我们根据NCBI和HapMap数据库中已有的PDLIM5基因的信息和以往的研究,选择了SNPs位点,并用软件设计了引物。接着我们在江西地区中国汉族人群的精神分裂症病例对照样本中,用单碱基延伸的试验方法获取了样本PDLIM5基因上六个常见单核苷酸多态性位点的基因型,并根据病例对照组样本的特点和基因型的结果,用COCAPHASE和Hapview等软件统计分析,根据统计结果估计精神分裂症与PDLIM5之间是否存在关联。所选的六个单核苷酸多态性位点中,rs2433322在病例组和对照组中的等位基因频率有显著性差异(P=0.000010),包含这个位点的单倍型也同样发现存在显著性差异(在邦弗朗尼校正后Global P=0.00019)。我们的结果支持了PDLIM5很可能是精神分裂症的易感基因之一的假设。
Schizophrenia is a chronic, severe mental disorder that affects approximately 1% of the world’s population. The disorder is characterized by psychotic symptoms and by cognitive, affective, and psychosocial impairment. Studies of family, twin, and adoption reveal that genetic factors play an important role in the etiological complex of schizophrenia. The inheritance pattern of schizophrenia suggests that there are multiple susceptibility genes, each with individually small effects, which interact with one another and with environmental factors to influence susceptibility to the diseases. In this thesis, we investigated associations between the susceptibility genes and schizophrenia (KIF2 and PDLIM5) in the Chinese Han population using geomic techniques.
KIF2 belongs to the kinesin-like protein family and regulates microtubule dynamics at the growth cone edge by depolymerizing microtubules. It plays an important role in the suppression of collateral branch extension. On the other hand, KIF2 is a motor for anterograde transport, and plays an important role in expansion at the nerve growth cone. Homma et al. in 2003 reported that Kif2a knockout mice showed many brain abnormalities, especially in the CA1 and CA3 fields of hippocampal pyramidal cells which are associated with many mental disorders. The extension of collateral growth cones is suppressed in Kif2a+/+ and Kif2a-/- cultured neuron extends more long collaterals without the suppression of Kif2a. Therefore, KIF2 might be one of the susceptible genes of schizophrenia with functional susceptibility. KIF2, the orthologue of Kif2a, maps on 5q12.1 in human genome. On the basis of that KIF2 may be a potential candidate gene for schizophrenia, we selected four common SNPs in the region of KIF2 according to the data in NCBI database and designed appropriate primers for these SNPs. Then we acquired the genotypes of four common SNPs in the sample of 280 nuclear family of the Chinese Han population using the allele specific PCR technology, and studied the association relationship between the KIF2 gene and schizophrenia using ETDT, 2LD, Hapview and FBAT softwares. None of the four markers we selected in the KIF2 gene revealed transmission distortion in the trios. However, a common two-SNP haplotype (rs2289883/rs464058, G/A) showed a significant association with schizophrenia. In addition, a four-SNP haplotype (T/G/A/G) with a frequency of 23.4%, which was identified in parental chromosomes, showed a significant association with schizophrenia (P = 0.00795). Our results demonstrate that the KIF2 gene, located at 5q12.1, is a potential schizophrenia susceptibility gene. The PDZ and LIM domain 5 protein (PDLIM5) contains one PDZ (postsynaptic density-95/discs large/zone occludens-1) domain and three LIM (Lin-11, Isl-1, and Mec-3) domains, which is also thought as enigma-homologue LIM domain (ENH) protein or LIM protein. As a member of the Enigma class of proteins, LIM domain containing protein is involved in cytoskeleton organization, cell lineage specification, organ development, and oncogenesis. The enigma-homologue LIM domain (ENH) protein was expressed in various regions of the brain, most notably in the hippocampi, cortex, thalamus, hypothalamus, amygdala, and cerebellum. In hippocampal neurons, ENH appears to be localized in presynaptic nerve terminals. PDLIM5 is also a homolog of the AD-associated neuronal thread protein (AD7c-NTP), which is over-expressed in Alzheimer disease sufferers, beginning early in the course of the disease. Iwamoto et al. compared the mRNA levels of PDLIM5 in the lymphoblastoid cell lines (LCLs) and postmortem brains of subjects with mental disorders with those of controls. They found that the mRNA level of PDLIM5 was decreased in the lymphoblastoid cells derived from patients with schizophrenia and bipolar disorders, but commonly increased in the postmortem brains of patients with schizophrenia, bipolar disorders, and major depression. Moreover, Kato et al. provided confirmation of up-regulation of the mRNA level of PDLIM5 in an independent brain sample set obtained from the Stanley Array Collection. On the other hand, PDLIM5 is located on human chromosome 4q22.3, which was suggested a hotspot region with susceptibility genes of schizophrenia by several independent linkage studies. These evidences imply that PDLIM5 is a potential susceptible gene for schizophrenia. In this work, we selected six common SNPs in the region of PDLIM5 according to the previous studies and the information of PDLIM5 in NCBI and HapMap databases and designed appropriate primers for these SNPs. Then we acquired the genotypes of the six common SNPs in the case-control samples of Jiangxi province using the single nucleotide primer extension method, and studied the association relationship between the PDLIM5 gene and schizophrenia using Hapview and COCAPHSE softwares. Among six SNPs we selected, rs2433322 showed significantly different frequencies between cases and controls (P=0.000010). Haplotypes constructed by rs2433322 were also significantly associated with schizophrenia (Global P=0.00019 even after strict Bonferroni correction). Our results provide further evidence to support PDLIM5 as a potential susceptible gene for schizophrenia.
KIF2是动力蛋白Kinesin家族的一员,在哺乳动物的神经元生长过程中承担重要的转运膜复合体和蛋白复合体的作用,并且通过在生长锥的边缘解聚微管调节微管动力。Homma等报道Kif2a基因敲除的小鼠在海马体的CA1和CA3区域出现了不正常的松散排列;而且在海马神经元的体外培养实验中,Kif2a-/-的海马神经元细胞在缺失了KIF2蛋白的抑制侧枝生长后较野生型神经元细胞长出很多侧枝。因此,KIF2很有可能是精神分裂症的易感基因之一,具有功能候选的特性。小鼠Kif2基因的同源基因在人类基因组的5q12.1。为了检测KIF2基因与精神分裂症发病的相关性,我们根据NCBI数据库中已有的KIF2基因的信息,选择了四个常见高频率单核苷酸多态性(Single Nucleotide Polymorphism,SNP)位点,并用软件设计了PCR引物,在中国汉族人群280个核心家系样本中,用等位基因实时PCR技术试验获得了样本所选四个位点的基因型,进而根据基因型数据和家系样本的结构,用ETDT、2LD、Hapview和FBAT软件分析了KIF2基因和精神分裂症的相关性。所选四个常见SNPs位点的关联分析中没有得到任何显著性结果。然而,本研究发现一个2-SNP的核心区域(rs2289883/rs464058,G/A)单倍型分析结果与精神分裂症密切相关;此外研究发现一个拥有23.4%的频率的常见4-SNP的单倍型(T/G/A/G)与精神分裂症相关(P=0.00795)。实验结果支持了KIF2基因是精神分裂症的易感基因之一的假设。
PDLIM5是一个LIM结构域的蛋白,在细胞骨架的组织,细胞系的分化,器官发育和肿瘤形成中都有重要作用。这个蛋白同时也是Enigma蛋白家族中的一员,具有典型的由N端PDZ结构域和C端的1-3个LIM结构域构成的典型特征。PDLIM5蛋白在大脑的许多区域都有表达,包括海马体,皮层,丘脑,丘脑下部,杏仁体和小脑。在海马的神经元上,PDLIM5蛋白分布在突触后,是阿尔茨海默症发病期过渡表达蛋白AD7c-NTP的同源蛋白。Iwamoto等研究者发现在精神分裂症和双向情感障碍的患者的淋巴细胞系中,PDLIM5的mRNAs的量较正常人的量偏低,但是在精神分裂症、双向情感障碍以及抑郁症的患者的脑中,PDLIM5的mRNAs的量较正常人偏高。Kato等研究者报道了PDLIM5 mRNA在精神分裂症和双向情感障碍的患者脑中表达上调。从基因组研究的角度上,PDLIM5定位于人类基因组的4q22.3的位置,这一区域已经被多个连锁研究证明是精神分裂症的阳性区域。以上蛋白功能方面和连锁方面的证据提示,PDLIM5可能是精神分裂症的易感基因之一。因此,我们根据NCBI和HapMap数据库中已有的PDLIM5基因的信息和以往的研究,选择了SNPs位点,并用软件设计了引物。接着我们在江西地区中国汉族人群的精神分裂症病例对照样本中,用单碱基延伸的试验方法获取了样本PDLIM5基因上六个常见单核苷酸多态性位点的基因型,并根据病例对照组样本的特点和基因型的结果,用COCAPHASE和Hapview等软件统计分析,根据统计结果估计精神分裂症与PDLIM5之间是否存在关联。所选的六个单核苷酸多态性位点中,rs2433322在病例组和对照组中的等位基因频率有显著性差异(P=0.000010),包含这个位点的单倍型也同样发现存在显著性差异(在邦弗朗尼校正后Global P=0.00019)。我们的结果支持了PDLIM5很可能是精神分裂症的易感基因之一的假设。
Schizophrenia is a chronic, severe mental disorder that affects approximately 1% of the world’s population. The disorder is characterized by psychotic symptoms and by cognitive, affective, and psychosocial impairment. Studies of family, twin, and adoption reveal that genetic factors play an important role in the etiological complex of schizophrenia. The inheritance pattern of schizophrenia suggests that there are multiple susceptibility genes, each with individually small effects, which interact with one another and with environmental factors to influence susceptibility to the diseases. In this thesis, we investigated associations between the susceptibility genes and schizophrenia (KIF2 and PDLIM5) in the Chinese Han population using geomic techniques.
KIF2 belongs to the kinesin-like protein family and regulates microtubule dynamics at the growth cone edge by depolymerizing microtubules. It plays an important role in the suppression of collateral branch extension. On the other hand, KIF2 is a motor for anterograde transport, and plays an important role in expansion at the nerve growth cone. Homma et al. in 2003 reported that Kif2a knockout mice showed many brain abnormalities, especially in the CA1 and CA3 fields of hippocampal pyramidal cells which are associated with many mental disorders. The extension of collateral growth cones is suppressed in Kif2a+/+ and Kif2a-/- cultured neuron extends more long collaterals without the suppression of Kif2a. Therefore, KIF2 might be one of the susceptible genes of schizophrenia with functional susceptibility. KIF2, the orthologue of Kif2a, maps on 5q12.1 in human genome. On the basis of that KIF2 may be a potential candidate gene for schizophrenia, we selected four common SNPs in the region of KIF2 according to the data in NCBI database and designed appropriate primers for these SNPs. Then we acquired the genotypes of four common SNPs in the sample of 280 nuclear family of the Chinese Han population using the allele specific PCR technology, and studied the association relationship between the KIF2 gene and schizophrenia using ETDT, 2LD, Hapview and FBAT softwares. None of the four markers we selected in the KIF2 gene revealed transmission distortion in the trios. However, a common two-SNP haplotype (rs2289883/rs464058, G/A) showed a significant association with schizophrenia. In addition, a four-SNP haplotype (T/G/A/G) with a frequency of 23.4%, which was identified in parental chromosomes, showed a significant association with schizophrenia (P = 0.00795). Our results demonstrate that the KIF2 gene, located at 5q12.1, is a potential schizophrenia susceptibility gene. The PDZ and LIM domain 5 protein (PDLIM5) contains one PDZ (postsynaptic density-95/discs large/zone occludens-1) domain and three LIM (Lin-11, Isl-1, and Mec-3) domains, which is also thought as enigma-homologue LIM domain (ENH) protein or LIM protein. As a member of the Enigma class of proteins, LIM domain containing protein is involved in cytoskeleton organization, cell lineage specification, organ development, and oncogenesis. The enigma-homologue LIM domain (ENH) protein was expressed in various regions of the brain, most notably in the hippocampi, cortex, thalamus, hypothalamus, amygdala, and cerebellum. In hippocampal neurons, ENH appears to be localized in presynaptic nerve terminals. PDLIM5 is also a homolog of the AD-associated neuronal thread protein (AD7c-NTP), which is over-expressed in Alzheimer disease sufferers, beginning early in the course of the disease. Iwamoto et al. compared the mRNA levels of PDLIM5 in the lymphoblastoid cell lines (LCLs) and postmortem brains of subjects with mental disorders with those of controls. They found that the mRNA level of PDLIM5 was decreased in the lymphoblastoid cells derived from patients with schizophrenia and bipolar disorders, but commonly increased in the postmortem brains of patients with schizophrenia, bipolar disorders, and major depression. Moreover, Kato et al. provided confirmation of up-regulation of the mRNA level of PDLIM5 in an independent brain sample set obtained from the Stanley Array Collection. On the other hand, PDLIM5 is located on human chromosome 4q22.3, which was suggested a hotspot region with susceptibility genes of schizophrenia by several independent linkage studies. These evidences imply that PDLIM5 is a potential susceptible gene for schizophrenia. In this work, we selected six common SNPs in the region of PDLIM5 according to the previous studies and the information of PDLIM5 in NCBI and HapMap databases and designed appropriate primers for these SNPs. Then we acquired the genotypes of the six common SNPs in the case-control samples of Jiangxi province using the single nucleotide primer extension method, and studied the association relationship between the PDLIM5 gene and schizophrenia using Hapview and COCAPHSE softwares. Among six SNPs we selected, rs2433322 showed significantly different frequencies between cases and controls (P=0.000010). Haplotypes constructed by rs2433322 were also significantly associated with schizophrenia (Global P=0.00019 even after strict Bonferroni correction). Our results provide further evidence to support PDLIM5 as a potential susceptible gene for schizophrenia.
引文
1. 季建林, 《精神医学》, 复旦大学出版社. 2003.
2. 中华医学会精神科分会, 《中国精神障碍分类与诊断标准(第三版)》(CCMD-3), 山东科学技术出版社. 2001.
3. American Psychiatric Association Diagnostic and statistical manual of mental disorders, Washington, DC. American Psychiatric Press. 1987; DSM-Ⅲ-R, 3d ed, rev.
4. Chen, l. h. 1998.
5. Gottesman, I. I., Schizophrenia Genesis: The Origins of Madness, WH Freeman. 1991.
6. Cloninger, C. R., The discovery of susceptibility genes for mental disorders, Proc Natl Acad Sci U S A. 2002;99:13365-7.
7. Risch, N., Linkage strategies for genetically complex traits. II. The power of affected relative pairs, Am J Hum Genet. 1990;46:229-41.
8. O'Donovan, M. C., Williams, N. M., et al., Recent advances in the genetics of schizophrenia, Hum Mol Genet. 2003;12 Spec No 2:R125-33.
9. Gottesman, I. I. and Wolfgram, D. L., Schizophrenia genesis : the origins of madness, A Series of books in psychology. 1991:xiii,296p.
10. Geddes, J. R. and Lawrie, S. M., Obstetric complications and schizophrenia: a meta-analysis, Br J Psychiatry. 1995;167:786-93.
11. St Clair, D., Xu, M., et al., Rates of adult schizophrenia following prenatal exposure to the Chinese famine of 1959-1961, Jama. 2005;294:557-62.
12. Susser, E. S. and Lin, S. P., Schizophrenia after prenatal exposure to the Dutch Hunger Winter of 1944-1945, Arch Gen Psychiatry. 1992;49:983-8.
13. O'Callaghan, E., Gibson, T., et al., Season of birth in schizophrenia. Evidence for confinement of an excess of winter births to patients without a family history of mental disorder, Br J Psychiatry. 1991;158:764-9.
14. Pulver, A. E., Liang, K. Y., et al., Risk factors in schizophrenia. Season of birth, gender, and familial risk, Br J Psychiatry. 1992;160:65-71.
15. Hudson, C. G., Socioeconomic status and mental illness: tests of the social causation and selection hypotheses, Am J Orthopsychiatry. 2005;75:3-18.
16. Harrison PJ, W. D., Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence, Mol Psychiatry. 2004.
17. Rapoport, J. L., Addington, A. M., et al., The neurodevelopmental model of schizophrenia: update 2005, Mol Psychiatry. 2005.
18. Sullivan, E. V., Shear, P. K., et al., Cognitive and motor impairments are related to gray matter volume deficits in schizophrenia, Biol Psychiatry. 1996;39:234-40.
19. Lawrie, S. M. and Abukmeil, S. S., Brain abnormality in schizophrenia. A systematic and quantitative review of volumetric magnetic resonance imaging studies, Br J Psychiatry. 1998;172:110-20.
20. Thompson, P. M., Vidal, C., et al., Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia, Proc Natl Acad Sci U S A. 2001;98:11650-5.
21. Wilke, M., Kaufmann, C., et al., Gray matter-changes and correlates of disease severity in schizophrenia: a statistical parametric mapping study, Neuroimage. 2001;13:814-24.
22. Suzuki, M., Nohara, S., et al., Regional changes in brain gray and white matter in patients with schizophrenia demonstrated with voxel-based analysis of MRI, Schizophr Res. 2002;55:41-54.
23. Hulshoff Pol, H. E., Schnack, H. G., et al., Volume changes in gray matter in patients with schizophrenia, Am J Psychiatry. 2002;159:244-50.
24. Suddath, R. L., Christison, G. W., et al., Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia, N Engl J Med. 1990;322:789-94.
25. Gaser, C., Nenadic, I., et al., Ventricular enlargement in schizophrenia related to volume reduction of the thalamus, striatum, and superior temporal cortex, Am J Psychiatry. 2004;161:154-6.
26. Berman KF and DR., W., Functional localization in the brain in schizophrenia. In: Review of Psychiatry, vol. 10, Tasman A and Goldfinger S (eds), Washington DC: American Psychiatric Press, . 1991:pp. 24–59.
27. Snyder, S. H., The dopamine hypothesis of schizophrenia: focus on the dopamine receptor, Am J Psychiatry. 1976;133:197-202.
28. Abi-Dargham, A., Gil, R., et al., Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort, Am J Psychiatry. 1998;155:761-7.
29. Breier, A., Su, T. P., et al., Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method, Proc Natl Acad Sci U S A. 1997;94:2569-74.
30. Laruelle, M., Abi-Dargham, A., et al., Increased dopamine transmission in schizophrenia: relationship to illness phases, Biol Psychiatry. 1999;46:56-72.
31. Snyder, S. H., Amphetamine psychosis: a "model" schizophrenia mediated by catecholamines, Am J Psychiatry. 1973;130:61-7.
32. Creese, I., Burt, D. R., et al., Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs, Science. 1976;192:481-3.
33. Carlsson, A., The current status of the dopamine hypothesis of schizophrenia, Neuropsychopharmacology. 1988;1:179-86.
34. Balestrieri, A. and Fontanari, D., Acquired and crossed tolerance to mescaline, LSD-25, and BOL-148, Arch Gen Psychiatry. 1959;1:279-82.
35. Shaw, E. and Woolley, D. W., Some serotoninlike activities of lysergic acid diethylamide, Science. 1956;124:121-2.
36. 沈渔邨, 《精神病学(第三版)》, 北京,人民卫生出版社. 1994.
37. William M, S. P., Marggy GF, Noradrenergic function in schizophrenia, Arch Gen Psychiatry. 1987;44:898-914.
38. 金卫东,刘铁榜,臧德馨, 精神分裂症中枢神经介质假说的修正和发展, 中华神经精神科杂志. 1992;25:55-7.
39. Lucas-Meunier, E., Fossier, P., et al., Cholinergic modulation of the cortical neuronal network, Pflugers Arch. 2003;446:17-29.
40. 杜雨苍, 《神经肽与脑功能》, 上海, 上海科技教育出版社. 1998.
41. Botstein, D. and Risch, N., Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease, Nat Genet. 2003;33 Suppl:228-37.
42. Terwilliger, J. D. and Weiss, K. M., Linkage disequilibrium mapping of complex disease: fantasy or reality?, Curr Opin Biotechnol. 1998;9:578-94.
43. Cardon, L. R. and Bell, J. I., Association study designs for complex diseases, Nat Rev Genet. 2001;2:91-9.
44. Ott, J., Analysis of Human Genetic Linkage, The Johns Hopkins University Press. Third Edition.
45. Yang, X., She, C., et al., A locus for brachydactyly type A-1 maps to chromosome 2q35-q36, Am J Hum Genet. 2000;66:892-903.
46. Gao, B., Guo, J., et al., Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-1, Nat Genet. 2001;28:386-8.
47. Ardlie, K. G., Kruglyak, L., et al., Patterns of linkage disequilibrium in the human genome, Nat Rev Genet. 2002;3:299-309.
48. Pritchard, J. K. and Przeworski, M., Linkage disequilibrium in humans: models and data, Am J Hum Genet. 2001;69:1-14.
49. Sham, P., Statistics in Human Genetics, Arnold. 1998.
50. Terwilliger, J. D., Zollner, S., et al., Mapping genes through the use of linkage disequilibrium generated by genetic drift: 'drift mapping' in small populations with no demographic expansion, Hum Hered. 1998;48:138-54.
51. Cordell, H. J. and Clayton, D. G., Genetic association studies, Lancet. 2005;366:1121-31.
52. Risch, N. and Teng, J., The relative power of family-based and case-control designs for linkage disequilibrium studies of complex human diseases I. DNA pooling, Genome Res. 1998;8:1273-88.
53. Pritchard, J. K. and Rosenberg, N. A., Use of unlinked genetic markers to detect population stratification in association studies, Am J Hum Genet. 1999;65:220-8.
54. Devlin, B. and Roeder, K., Genomic control for association studies, Biometrics. 1999;55:997-1004.
55. Bacanu, S. A., Devlin, B., et al., The power of genomic control, Am J Hum Genet. 2000;66:1933-44.
56. Falk, C. T. and Rubinstein, P., Haplotype relative risks: an easy reliable way to construct a proper control sample for risk calculations, Ann Hum Genet. 1987;51 ( Pt 3):227-33.
57. Terwilliger, J. D. and Ott, J., A haplotype-based 'haplotype relative risk' approach to detecting allelic associations, Hum Hered. 1992;42:337-46.
58. Spielman, R. S., McGinnis, R. E., et al., Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM), Am J Hum Genet. 1993;52:506-16.
59. Ott, J., Statistical properties of the haplotype relative risk, Genet Epidemiol. 1989;6:127-30.
60. Reich, D. E. and Lander, E. S., On the allelic spectrum of human disease, Trends Genet. 2001;17:502-10.
61. Becker, K. G., The common variants/multiple disease hypothesis of common complex genetic disorders, Med Hypotheses. 2004;62:309-17.
62. Smith, D. J. and Lusis, A. J., The allelic structure of common disease, Hum Mol Genet. 2002;11:2455-61.
63. Morton, N. E., Linkage disequilibrium maps and association mapping, J Clin Invest. 2005;115:1425-30.
64. Bearden, C. E., Reus, V. I., et al., Why genetic investigation of psychiatric disorders is so difficult, Curr Opin Genet Dev. 2004;14:280-6.
65. Risch, N. and Merikangas, K., The future of genetic studies of complex human diseases, Science. 1996;273:1516-7.
66. Carlson, C. S., Eberle, M. A., et al., Mapping complex disease loci in whole-genome association studies, Nature. 2004;429:446-52.
67. Johnson, G. C., Esposito, L., et al., Haplotype tagging for the identification of common disease genes, Nat Genet. 2001;29:233-7.
68. Zhang, K., Qin, Z. S., et al., Haplotype block partitioning and tag SNP selection using genotype data and their applications to association studies, Genome Res. 2004;14:908-16.
69. Reich, D. E., Cargill, M., et al., Linkage disequilibrium in the human genome, Nature. 2001;411:199-204.
70. Daly, M. J., Rioux, J. D., et al., High-resolution haplotype structure in the human genome, Nat Genet. 2001;29:229-32.
71. Jeffreys, A. J., Kauppi, L., et al., Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex, Nat Genet. 2001;29:217-22.
72. van den Oord, E. J. and Neale, B. M., Will haplotype maps be useful for finding genes?, Mol Psychiatry. 2004;9:227-36.
73. Wall, J. D. and Pritchard, J. K., Haplotype blocks and linkage disequilibrium in the human genome, Nat Rev Genet. 2003;4:587-97.
74. Patil, N., Berno, A. J., et al., Blocks of limited haplotype diversity revealed by high-resolution scanning of human chromosome 21, Science. 2001;294:1719-23.
75. Zhang, K., Deng, M., et al., A dynamic programming algorithm for haplotype block partitioning, Proc Natl Acad Sci U S A. 2002;99:7335-9.
76. Zhang, K., Calabrese, P., et al., Haplotype block structure and its applications to associationstudies: power and study designs, Am J Hum Genet. 2002;71:1386-94.
77. Gabriel, S. B., Schaffner, S. F., et al., The structure of haplotype blocks in the human genome, Science. 2002;296:2225-9.
78. Kruglyak, L., Prospects for whole-genome linkage disequilibrium mapping of common disease genes, Nat Genet. 1999;22:139-44.
79. The International HapMap Project, Nature. 2003;426:789-96.
80. Integrating ethics and science in the International HapMap Project, Nat Rev Genet. 2004;5:467-75.
81. Altshuler, D., Brooks, L. D., et al., A haplotype map of the human genome, Nature. 2005;437:1299-320.
82. Sham, P. C. and Curtis, D., Monte Carlo tests for associations between disease and alleles at highly polymorphic loci, Ann Hum Genet. 1995;59 ( Pt 1):97-105.
83. Xie, X. and Ott, J., Testing linkage disequilibrium between a disease gene and marker loci, Am J Hum Genet. 1993;53:1107.
84. Zhao, J. H., Curtis, D., et al., Model-free analysis and permutation tests for allelic associations, Hum Hered. 2000;50:133-9.
85. Zhao, J. H. and Sham, P. C., Faster haplotype frequency estimation using unrelated subjects, Hum Hered. 2002;53:36-41.
86. Schneider, S., Roessli, D., et al., Arlequin: A software for population genetics data analysis. Ver 2.000, Genetics and Biometry Lab, Dept. of Anthropology, University of Geneva. 2000.
87. Stephens, M., Smith, N. J., et al., A new statistical method for haplotype reconstruction from population data, Am J Hum Genet. 2001;68:978-89.
88. Niu, T., Qin, Z. S., et al., Bayesian haplotype inference for multiple linked single-nucleotide polymorphisms, Am J Hum Genet. 2002;70:157-69.
89. Sham, P. C. and Curtis, D., An extended transmission/disequilibrium test (TDT) for multi-allele marker loci, Ann Hum Genet. 1995;59 ( Pt 3):323-36.
90. Clayton, D., A generalization of the transmission/disequilibrium test for uncertain-haplotype transmission, Am J Hum Genet. 1999;65:1170-7.
91. Horvath, S., Xu, X., et al., Family-based tests for associating haplotypes with general phenotype data: application to asthma genetics, Genet Epidemiol. 2004;26:61-9.
92. Laird, N. M., Horvath, S., et al., Implementing a unified approach to family-based tests of association, Genet Epidemiol. 2000;19 Suppl 1:S36-42.
93. Dudbridge, F., Pedigree disequilibrium tests for multilocus haplotypes, Genet Epidemiol. 2003;25:115-21.
94. Barrett, J. C., Fry, B., et al., Haploview: analysis and visualization of LD and haplotype maps, Bioinformatics. 2005;21:263-5.
95. Sklar, P., Linkage analysis in psychiatric disorders: the emerging picture, Annu Rev Genomics Hum Genet. 2002;3:371-413.
96. Mirnics, K., Middleton, F. A., et al., Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex, Neuron. 2000;28:53-67.
97. Larminie, C., Murdock, P., et al., Selective expression of regulators of G-protein signaling (RGS) in the human central nervous system, Brain Res Mol Brain Res. 2004;122:24-34.
98. Ross, E. M. and Wilkie, T. M., GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins, Annu Rev Biochem. 2000;69:795-827.
99. Chowdari, K. V., Mirnics, K., et al., Association and linkage analyses of RGS4 polymorphisms in schizophrenia, Hum Mol Genet. 2002;11:1373-80.
100. Fallin, M. D., Lasseter, V. K., et al., Bipolar I disorder and schizophrenia: a 440-single-nucleotide polymorphism screen of 64 candidate genes among Ashkenazi Jewish case-parent trios, Am J Hum Genet. 2005;77:918-36.
101. Chen, X., Dunham, C., et al., Regulator of G-protein signaling 4 (RGS4) gene is associated with schizophrenia in Irish high density families, Am J Med Genet. 2004;129B:23-6.
102. Zhang, F., St Clair, D., et al., Association analysis of the RGS4 gene in Han Chinese and Scottish populations with schizophrenia, Genes Brain Behav. 2005;4:444-8.
103. Sobell, J. L., Richard, C., et al., Failure to confirm association between RGS4 haplotypes and schizophrenia in Caucasians, Am J Med Genet B Neuropsychiatr Genet. 2005;139:23-7.
104. Millar, J. K., Wilson-Annan, J. C., et al., Disruption of two novel genes by a translocation co-segregating with schizophrenia, Hum Mol Genet. 2000;9:1415-23.
105. Ekelund, J., Hovatta, I., et al., Chromosome 1 loci in Finnish schizophrenia families, Hum Mol Genet. 2001;10:1611-7.
106. Hennah, W., Varilo, T., et al., Haplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects, Hum Mol Genet. 2003;12:3151-9.
107. Callicott, J. H., Straub, R. E., et al., Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia, Proc Natl Acad Sci U S A. 2005;102:8627-32.
108. Hodgkinson, C. A., Goldman, D., et al., Disrupted in Schizophrenia 1 (DISC1): Association with Schizophrenia, Schizoaffective Disorder, and Bipolar Disorder, Am J Hum Genet. 2004;75:862-72.
109. Sachs, N. A., Sawa, A., et al., A frameshift mutation in Disrupted in Schizophrenia 1 in an American family with schizophrenia and schizoaffective disorder, Mol Psychiatry. 2005;10:758-64.
110. Millar, J. K., Pickard, B. S., et al., DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling, Science. 2005;310:1187-91.
111. Kamiya, A., Kubo, K., et al., A schizophrenia-associated mutation of DISC1 perturbs cerebral cortex development, Nat Cell Biol. 2005;7:1167-78.
112. Sklar, P., Pato, M. T., et al., Genome-wide scan in Portuguese Island families identifies 5q31-5q35 as a susceptibility locus for schizophrenia and psychosis, Mol Psychiatry. 2004;9:213-8.
113. Petryshen, T. L., Middleton, F. A., et al., Genetic investigation of chromosome 5q GABA(A) receptor subunit genes in schizophrenia, Mol Psychiatry. 2005.
114. Roberts, E., Prospects for research on schizophrenia. An hypotheses suggesting that there is a defect in the GABA system in schizophrenia, Neurosci Res Program Bull. 1972;10:468-82.
115. Lewis, D. A., Hashimoto, T., et al., Cortical inhibitory neurons and schizophrenia, Nat Rev Neurosci. 2005;6:312-24.
116. Pimm, J., McQuillin, A., et al., The Epsin 4 gene on chromosome 5q, which encodes the clathrin-associated protein enthoprotin, is involved in the genetic susceptibility to schizophrenia, Am J Hum Genet. 2005;76:902-7.
117. Wasiak, S., Legendre-Guillemin, V., et al., Enthoprotin: a novel clathrin-associated protein identified through subcellular proteomics, J Cell Biol. 2002;158:855-62.
118. Straub, R. E., MacLean, C. J., et al., A potential vulnerability locus for schizophrenia on chromosome 6p24-22: evidence for genetic heterogeneity, Nat Genet. 1995;11:287-93.
119. Straub, R. E., Jiang, Y., et al., Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia, Am J Hum Genet. 2002;71:337-48.
120. Schwab, S. G., Knapp, M., et al., Support for association of schizophrenia with genetic variation in the 6p22.3 gene, dysbindin, in sib-pair families with linkage and in an additional sample of triad families, Am J Hum Genet. 2003;72:185-90.
121. Tang, J. X., Zhou, J., et al., Family-based association study of DTNBP1 in 6p22.3 and schizophrenia, Mol Psychiatry. 2003;8:717-8.
122. Kirov, G., Ivanov, D., et al., Strong evidence for association between the dystrobrevin binding protein 1 gene (DTNBP1) and schizophrenia in 488 parent-offspring trios from Bulgaria, Biol Psychiatry. 2004;55:971-5.
123. Hall, D., Gogos, J. A., et al., The contribution of three strong candidate schizophrenia susceptibility genes in demographically distinct populations, Genes Brain Behav. 2004;3:240-8.
124. De Luca, V., Voineskos, D., et al., Untranslated region haplotype in dysbindin gene: analysis in schizophrenia, J Neural Transm. 2005;112:1263-7.
125. Li, W., Zhang, Q., et al., Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1), Nat Genet. 2003;35:84-9.
126. Benson, M. A., Newey, S. E., et al., Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain, J Biol Chem. 2001;276:24232-41.
127. Talbot, K., Eidem, W. L., et al., Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia, J Clin Invest. 2004;113:1353-63.
128. Weickert, C. S., Straub, R. E., et al., Human dysbindin (DTNBP1) gene expression in normal brain and in schizophrenic prefrontal cortex and midbrain, Arch Gen Psychiatry. 2004;61:544-55.
129. Numakawa, T., Yagasaki, Y., et al., Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia, Hum Mol Genet. 2004;13:2699-708.
130. Levinson, D. F., Holmans, P., et al., Multicenter linkage study of schizophrenia candidate regions on chromosomes 5q, 6q, 10p, and 13q: schizophrenia linkage collaborative group III, Am J Hum Genet. 2000;67:652-63.
131. Duan, J., Martinez, M., et al., Polymorphisms in the trace amine receptor 4 (TRAR4) gene on chromosome 6q23.2 are associated with susceptibility to schizophrenia, Am J Hum Genet. 2004;75:624-38.
132. Duan, S., Du, J., et al., Failure to find association between TRAR4 and schizophrenia in the Chinese Han population, J Neural Transm. 2005.
133. Ikeda, M., Iwata, N., et al., No association of haplotype-tagging SNPs in TRAR4 with schizophrenia in Japanese patients, Schizophr Res. 2005;78:127-30.
134. Borowsky, B., Adham, N., et al., Trace amines: identification of a family of mammalian G protein-coupled receptors, Proc Natl Acad Sci U S A. 2001;98:8966-71.
135. Abou Jamra, R., Sircar, I., et al., A family-based and case-control association study of trace amine receptor genes on chromosome 6q23 in bipolar affective disorder, Mol Psychiatry. 2005;10:618-20.
136. Marti, S. B., Cichon, S., et al., Metabotropic glutamate receptor 3 (GRM3) gene variation is not associated with schizophrenia or bipolar affective disorder in the German population, Am J Med Genet. 2002;114:46-50.
137. Fujii, Y., Shibata, H., et al., Positive associations of polymorphisms in the metabotropic glutamate receptor type 3 gene (GRM3) with schizophrenia, Psychiatr Genet. 2003;13:71-6.
138. Egan, M. F., Straub, R. E., et al., Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia, Proc Natl Acad Sci U S A. 2004;101:12604-9.
139. Chen, Q., He, G., et al., A case-control study of the relationship between the metabotropic glutamate receptor 3 gene and schizophrenia in the Chinese population, Schizophr Res. 2005;73:21-6.
140. Norton, N., Williams, H. J., et al., No evidence for association between polymorphisms in GRM3 and schizophrenia, BMC Psychiatry. 2005;5:23.
141. Gerber, D. J., Hall, D., et al., Evidence for association of schizophrenia with genetic variation in the 8p21.3 gene, PPP3CC, encoding the calcineurin gamma subunit, Proc Natl Acad Sci U S A. 2003;100:8993-8.
142. Eastwood, S. L., Burnet, P. W., et al., Decreased hippocampal expression of the susceptibility gene PPP3CC and other calcineurin subunits in schizophrenia, Biol Psychiatry. 2005;57:702-10.
143. Miyakawa, T., Leiter, L. M., et al., Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia, Proc Natl Acad Sci U S A. 2003;100:8987-92.
144. Corfas, G., Roy, K., et al., Neuregulin 1-erbB signaling and the molecular/cellular basis of schizophrenia, Nat Neurosci. 2004;7:575-80.
145. Stefansson, H., Sigurdsson, E., et al., Neuregulin 1 and susceptibility to schizophrenia, Am J Hum Genet. 2002;71:877-92.
146. Stefansson, H., Sarginson, J., et al., Association of neuregulin 1 with schizophrenia confirmed in a Scottish population, Am J Hum Genet. 2003;72:83-7.
147. Yang, J. Z., Si, T. M., et al., Association study of neuregulin 1 gene with schizophrenia, Mol Psychiatry. 2003;8:706-9.
148. Zhao, X., Shi, Y., et al., A case control and family based association study of the neuregulin1 gene and schizophrenia, J Med Genet. 2004;41:31-4.
149. Li, T., Stefansson, H., et al., Identification of a novel neuregulin 1 at-risk haplotype in Han schizophrenia Chinese patients, but no association with the Icelandic/Scottish risk haplotype, Mol Psychiatry. 2004;9:698-704.
150. Thiselton, D. L., Webb, B. T., et al., No evidence for linkage or association of neuregulin-1 (NRG1) with disease in the Irish study of high-density schizophrenia families (ISHDSF), Mol Psychiatry. 2004;9:729.
151. Duan, J., Martinez, M., et al., Neuregulin 1 ( NRG1 ) and schizophrenia: analysis of a US family sample and the evidence in the balance, Psychol Med. 2005;35:1599-610.
152. Badner, J. A. and Gershon, E. S., Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia, Mol Psychiatry. 2002;7:405-11.
153. Detera-Wadleigh, S. D., Badner, J. A., et al., A high-density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2, Proc Natl Acad Sci U S A. 1999;96:5604-9.
154. Chumakov, I., Blumenfeld, M., et al., Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia, Proc Natl Acad Sci U S A. 2002;99:13675-80.
155. Mothet, J. P., Parent, A. T., et al., D-serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor, Proc Natl Acad Sci U S A. 2000;97:4926-31.
156. Hattori, E., Liu, C., et al., Polymorphisms at the G72/G30 gene locus, on 13q33, are associated with bipolar disorder in two independent pedigree series, Am J Hum Genet. 2003;72:1131-40.
157. Schumacher, J., Jamra, R. A., et al., Examination of G72 and D-amino-acid oxidase as genetic risk factors for schizophrenia and bipolar affective disorder, Mol Psychiatry. 2004;9:203-7.
158. Wang, X., He, G., et al., Association of G72/G30 with schizophrenia in the Chinese population, Biochem Biophys Res Commun. 2004;319:1281-6.
159. Addington, A. M., Gornick, M., et al., Polymorphisms in the 13q33.2 gene G72/G30 are associated with childhood-onset schizophrenia and psychosis not otherwise specified, Biol Psychiatry. 2004;55:976-80.
160. Korostishevsky, M., Kaganovich, M., et al., Is the G72/G30 locus associated with schizophrenia? single nucleotide polymorphisms, haplotypes, and gene expression analysis, Biol Psychiatry. 2004;56:169-76.
161. Korostishevsky, M., Kremer, I., et al., Transmission disequilibrium and haplotype analyses of the G72/G30 locus: Suggestive linkage to schizophrenia in Palestinian Arabs living in the North ofIsrael, Am J Med Genet B Neuropsychiatr Genet. 2005.
162. Mulle, J. G., Chowdari, K. V., et al., No evidence for association to the G72/G30 locus in an independent sample of schizophrenia families, Mol Psychiatry. 2005;10:431-3.
163. Zou, F., Li, C., et al., A family-based study of the association between the G72/G30 genes and schizophrenia in the Chinese population, Schizophr Res. 2005;73:257-61.
164. Emamian, E. S., Hall, D., et al., Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia, Nat Genet. 2004;36:131-7.
165. Ohtsuki, T., Inada, T., et al., Failure to confirm association between AKT1 haplotype and schizophrenia in a Japanese case-control population, Mol Psychiatry. 2004;9:981-3.
166. Ikeda, M., Iwata, N., et al., Positive association of AKT1 haplotype to Japanese methamphetamine use disorder, Int J Neuropsychopharmacol. 2005:1-5.
167. Schwab, S. G., Hoefgen, B., et al., Further evidence for association of variants in the AKT1 gene with schizophrenia in a sample of European sib-pair families, Biol Psychiatry. 2005;58:446-50.
168. Lewis, C. M., Levinson, D. F., et al., Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia, Am J Hum Genet. 2003;73:34-48.
169. Karayiorgou, M., Morris, M. A., et al., Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11, Proc Natl Acad Sci U S A. 1995;92:7612-6.
170. Pulver, A. E., Nestadt, G., et al., Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives, J Nerv Ment Dis. 1994;182:476-8.
171. Murphy, K. C., Jones, L. A., et al., High rates of schizophrenia in adults with velo-cardio-facial syndrome, Arch Gen Psychiatry. 1999;56:940-5.
172. Liu, H., Heath, S. C., et al., Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia, Proc Natl Acad Sci U S A. 2002;99:3717-22.
173. Liu, H., Abecasis, G. R., et al., Genetic variation in the 22q11 locus and susceptibility to schizophrenia, Proc Natl Acad Sci U S A. 2002;99:16859-64.
174. Li, T., Ma, X., et al., Evidence for association between novel polymorphisms in the PRODH gene and schizophrenia in a Chinese population, Am J Med Genet. 2004;129B:13-5.
175. Williams, H. J., Williams, N., et al., Association between PRODH and schizophrenia is not confirmed, Mol Psychiatry. 2003;8:644-5.
176. Gothelf, D., Eliez, S., et al., COMT genotype predicts longitudinal cognitive decline and psychosis in 22q11.2 deletion syndrome, Nat Neurosci. 2005;8:1500-2.
177. Jacquet, H., Raux, G., et al., PRODH mutations and hyperprolinemia in a subset of schizophrenic patients, Hum Mol Genet. 2002;11:2243-9.
178. Jacquet, H., Demily, C., et al., Hyperprolinemia is a risk factor for schizoaffective disorder, Mol Psychiatry. 2005;10:479-85.
179. Bender, H. U., Almashanu, S., et al., Functional consequences of PRODH missense mutations, Am J Hum Genet. 2005;76:409-20.
180. Paterlini, M., Zakharenko, S. S., et al., Transcriptional and behavioral interaction between 22q11.2 orthologs modulates schizophrenia-related phenotypes in mice, Nat Neurosci. 2005;8:1586-94.
181. Weinshilboum, R. M., Otterness, D. M., et al., Methylation pharmacogenetics: catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase, Annu Rev Pharmacol Toxicol. 1999;39:19-52.
182. Lotta, T., Vidgren, J., et al., Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme, Biochemistry. 1995;34:4202-10.
183. Lachman, H. M., Papolos, D. F., et al., Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders, Pharmacogenetics. 1996;6:243-50.
184. Palmatier, M. A., Kang, A. M., et al., Global variation in the frequencies of functionally different catechol-O-methyltransferase alleles, Biol Psychiatry. 1999;46:557-67.
185. DeMille, M. M., Kidd, J. R., et al., Population variation in linkage disequilibrium across the COMT gene considering promoter region and coding region variation, Hum Genet. 2002;111:521-37.
186. Li, T., Sham, P. C., et al., Preferential transmission of the high activity allele of COMT in schizophrenia, Psychiatr Genet. 1996;6:131-3.
187. Li, T., Ball, D., et al., Family-based linkage disequilibrium mapping using SNP marker haplotypes: application to a potential locus for schizophrenia at chromosome 22q11, Mol Psychiatry. 2000;5:452.
188. Chen, X., Wang, X., et al., Variants in the catechol-o-methyltransferase (COMT) gene are associated with schizophrenia in Irish high-density families, Mol Psychiatry. 2004;9:962-7.
189. Egan, M. F., Goldberg, T. E., et al., Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia, Proc Natl Acad Sci U S A. 2001;98:6917-22.
190. Harrison, P. J. and Weinberger, D. R., Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence, Mol Psychiatry. 2004.
191. Chen, J., Lipska, B. K., et al., Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain, Am J Hum Genet. 2004;75:807-21.
192. Shifman, S., Bronstein, M., et al., A highly significant association between a COMT haplotype and schizophrenia, Am J Hum Genet. 2002;71:1296-302.
193. Mukai, J., Liu, H., et al., Evidence that the gene encoding ZDHHC8 contributes to the risk of schizophrenia, Nat Genet. 2004;36:725-31.
194. Chen, W. Y., Shi, Y. Y., et al., Case-control study and transmission disequilibrium test provide consistent evidence for association between schizophrenia and genetic variation in the 22q11 gene ZDHHC8, Hum Mol Genet. 2004;13:2991-5.
195. Glaser, B., Schumacher, J., et al., No association between the putative functional ZDHHC8 single nucleotide polymorphism rs175174 and schizophrenia in large European samples, Biol Psychiatry. 2005;58:78-80.
196. Addington, A. M., Gornick, M., et al., GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD(67)), is associated with childhood-onset schizophrenia and cortical gray matter volume loss, Mol Psychiatry. 2004.
197. Chen, Q., He, G., et al., Positive association between synapsin II and schizophrenia, Biol Psychiatry. 2004;56:177-81.
198. Chen, Q., He, G., et al., Family-Based Association Study of Synapsin II and Schizophrenia, Am J Hum Genet. 2004;75:873-7.
199. Neves-Pereira, M., Cheung, J. K., et al., BDNF gene is a risk factor for schizophrenia in a Scottish population, Mol Psychiatry. 2005;10:208-12.
200. Schumacher, J., Jamra, R. A., et al., Evidence for a relationship between genetic variants at the brain-derived neurotrophic factor (BDNF) locus and major depression, Biol Psychiatry. 2005;58:307-14.
201. Freedman, R., Adams, C. E., et al., The alpha7-nicotinic acetylcholine receptor and the pathology of hippocampal interneurons in schizophrenia, J Chem Neuroanat. 2000;20:299-306.
202. Leonard, S., Gault, J., et al., Association of promoter variants in the alpha7 nicotinic acetylcholine receptor subunit gene with an inhibitory deficit found in schizophrenia, Arch Gen Psychiatry. 2002;59:1085-96.
203. Sakowicz, R., Berdelis, M. S., et al., A marine natural product inhibitor of kinesin motors, Science. 1998;280:292-5.
204. Stewart, R. J., Thaler, J. P., et al., Direction of microtubule movement is an intrinsic property of the motor domains of kinesin heavy chain and Drosophila ncd protein, Proc Natl Acad Sci U S A. 1993;90:5209-13.
205. Goodson, H. V., Kang, S. J., et al., Molecular phylogeny of the kinesin family of microtubule motor proteins, J Cell Sci. 1994;107 ( Pt 7):1875-84.
206. VALE RD and RJ, F., The design plan of kinesin motors, Ann Rev Cell Dev Biol. 1977;13:745-77.
207. Hirokawa, N., Kinesin and dynein superfamily proteins and the mechanism of organelle transport, Science. 1998;279:519-26.
208. Lawrence, C. J., Dawe, R. K., et al., A standardized kinesin nomenclature, J Cell Biol. 2004;167:19-22.
209. Schnapp, B. J., Reese, T. S., et al., Kinesin is bound with high affinity to squid axon organelles that move to the plus-end of microtubules, J Cell Biol. 1992;119:389-99.
210. Hirose, K. and Amos, L. A., Three-dimensional structure of motor molecules, Cell Mol Life Sci. 1999;56:184-99.
211. Kull, F. J., Motor proteins of the kinesin superfamily: structure and mechanism. in Essays inBiochemistry.Molecular Motors edited Banting G, Higgins S.J., Portland Press. 2000;,London 61-73.
212. Howard, J., Molecular motors: structural adaptations to cellular functions, Nature. 1997;389:561-7.
213. Verhey, K. J., Lizotte, D. L., et al., Light chain-dependent regulation of Kinesin's interaction with microtubules, J Cell Biol. 1998;143:1053-66.
214. Weinberger, D. R., Berman, K. F., et al., Evidence of dysfunction of a prefrontal-limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins, Am J Psychiatry. 1992;149:890-7.
215. Csernansky, J. G., Wang, L., et al., Hippocampal deformities in schizophrenia characterized by high dimensional brain mapping, Am J Psychiatry. 2002;159:2000-6.
216. Kamiya, A., Tomoda, T., et al., DISC1-NDEL1/NUDEL protein interaction, an essential component for neurite outgrowth, is modulated by genetic variations of DISC1, Hum Mol Genet. 2006;15:3313-23.
217. Aizawa, H., Sekine, Y., et al., Kinesin family in murine central nervous system, J Cell Biol. 1992;119:1287-96.
218. American Psychiatric Association Diagnostic and statistical manual of mental disorders, DSM-Ⅲ-R, 3d ed, rev, Washington, DC. American Psychiatric Press. 1987.
219. Germer, S., Holland, M. J., et al., High-throughput SNP allele-frequency determination in pooled DNA samples by kinetic PCR, Genome Res. 2000;10:258-66.
220. Ye, S., Dhillon, S., et al., An efficient procedure for genotyping single nucleotide polymorphisms, Nucleic Acids Res. 2001;29:E88-8.
221. Zapata, C., Carollo, C., et al., Sampling variance and distribution of the D' measure of overall gametic disequilibrium between multiallelic loci, Ann Hum Genet. 2001;65:395-406.
222. Rabinowitz, D. and Laird, N., A unified approach to adjusting association tests for population admixture with arbitrary pedigree structure and arbitrary missing marker information, Hum Hered. 2000;50:211-23.
223. Barrett JC, Fry B, et al., Haploview: analysis and visualization of LD and haplotype maps, Bioinformatics. 2005;Jan.
224. Detera-Wadleigh, S. D., Goldin, L. R., et al., Exclusion of linkage to 5q11-13 in families with schizophrenia and other psychiatric disorders, Nature. 1989;340:391-3.
225. Mayor, C., Brudno, M., et al., VISTA : visualizing global DNA sequence alignments of arbitrary length, Bioinformatics. 2000;16:1046-7.
226. Schwartz, S., Elnitski, L., et al., MultiPipMaker and supporting tools: Alignments and analysis of multiple genomic DNA sequences, Nucleic Acids Res. 2003;31:3518-24.
227. Carter, K. W. and McCaskie, P. A., Linkage disequilibrium and haplotyping: applications to genetic epidemiology (Presentation, May 10th, 2005), Population Health Seminar Series, School of Population Health, The University of Western Australia. 2005.
228. Levinson, D. F., Mahtani, M. M., et al., Genome scan of schizophrenia, Am J Psychiatry. 1998;155:741-50.
229. Mowry, B. J., Ewen, K. R., et al., Second stage of a genome scan of schizophrenia: study of five positive regions in an expanded sample, Am J Med Genet. 2000;96:864-9.
230. Paunio, T., Tuulio-Henriksson, A., et al., Search for cognitive trait components of schizophrenia reveals a locus for verbal learning and memory on 4q and for visual working memory on 2q, Hum Mol Genet. 2004;13:1693-702.
231. Maeno-Hikichi, Y., Chang, S., et al., A PKC epsilon-ENH-channel complex specifically modulates N-type Ca2+ channels, Nat Neurosci. 2003;6:468-75.
232. Wu, M., Li, Y., et al., Cloning and identification of a novel human gene PDLIM5, a homolog of AD-associated neuronal thread protein (AD7c-NTP), DNA Seq. 2004;15:144-7.
233. Iwamoto, K., Kakiuchi, C., et al., Molecular characterization of bipolar disorder by comparing gene expression profiles of postmortem brains of major mental disorders, Mol Psychiatry. 2004;9:406-16.
234. Iwamoto, K., Bundo, M., et al., Expression of HSPF1 and LIM in the lymphoblastoid cells derived from patients with bipolar disorder and schizophrenia, J Hum Genet. 2004;49:227-31.
235. Kato, T., Iwayama, Y., et al., Gene expression and association analyses of LIM (PDLIM5) in bipolar disorder and schizophrenia, Mol Psychiatry. 2005;10:1045-55.
236. Horiuchi, Y., Arai, M., et al., A polymorphism in the PDLIM5 gene associated with gene expression and schizophrenia, Biol Psychiatry. 2006;59:434-9.
237. Sham, P. C. and Curtis, D., Monte Carlo tests for associations between disease and alleles at highly polymorphic loci, Ann Hum Genet. 1995;59:97-105.
238. Cordell, H. J. and Clayton, D. G., A unified stepwise regression procedure for evaluating the relative effects of polymorphisms within a gene using case/control or family data: application to HLA in type 1 diabetes, Am J Hum Genet. 2002;70:124-41.
239. Mander, A., Haplotype analysis in population-based association studies., STATA J. 2001;1:58-75.
240. Erdfelder, E., Faul, F., et al., G*Power: a general power analysis grogram, Behav Res Methods Instrum Comput. 1996;28:1-11.
241. Iga, J., Ueno, S., et al., Gene expression and association analysis of LIM (PDLIM5) in major depression, Neurosci Lett. 2006;400:203-7.
242. Risch, N., Burchard, E., et al., Categorization of humans in biomedical research: genes, race and disease, Genome Biol. 2002;3:comment2007.
243. Schulz, T. W., Nakagawa, T., et al., Actin/alpha-actinin-dependent transport of AMPA receptors in dendritic spines: role of the PDZ-LIM protein RIL, J Neurosci. 2004;24:8584-94.
2. 中华医学会精神科分会, 《中国精神障碍分类与诊断标准(第三版)》(CCMD-3), 山东科学技术出版社. 2001.
3. American Psychiatric Association Diagnostic and statistical manual of mental disorders, Washington, DC. American Psychiatric Press. 1987; DSM-Ⅲ-R, 3d ed, rev.
4. Chen, l. h. 1998.
5. Gottesman, I. I., Schizophrenia Genesis: The Origins of Madness, WH Freeman. 1991.
6. Cloninger, C. R., The discovery of susceptibility genes for mental disorders, Proc Natl Acad Sci U S A. 2002;99:13365-7.
7. Risch, N., Linkage strategies for genetically complex traits. II. The power of affected relative pairs, Am J Hum Genet. 1990;46:229-41.
8. O'Donovan, M. C., Williams, N. M., et al., Recent advances in the genetics of schizophrenia, Hum Mol Genet. 2003;12 Spec No 2:R125-33.
9. Gottesman, I. I. and Wolfgram, D. L., Schizophrenia genesis : the origins of madness, A Series of books in psychology. 1991:xiii,296p.
10. Geddes, J. R. and Lawrie, S. M., Obstetric complications and schizophrenia: a meta-analysis, Br J Psychiatry. 1995;167:786-93.
11. St Clair, D., Xu, M., et al., Rates of adult schizophrenia following prenatal exposure to the Chinese famine of 1959-1961, Jama. 2005;294:557-62.
12. Susser, E. S. and Lin, S. P., Schizophrenia after prenatal exposure to the Dutch Hunger Winter of 1944-1945, Arch Gen Psychiatry. 1992;49:983-8.
13. O'Callaghan, E., Gibson, T., et al., Season of birth in schizophrenia. Evidence for confinement of an excess of winter births to patients without a family history of mental disorder, Br J Psychiatry. 1991;158:764-9.
14. Pulver, A. E., Liang, K. Y., et al., Risk factors in schizophrenia. Season of birth, gender, and familial risk, Br J Psychiatry. 1992;160:65-71.
15. Hudson, C. G., Socioeconomic status and mental illness: tests of the social causation and selection hypotheses, Am J Orthopsychiatry. 2005;75:3-18.
16. Harrison PJ, W. D., Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence, Mol Psychiatry. 2004.
17. Rapoport, J. L., Addington, A. M., et al., The neurodevelopmental model of schizophrenia: update 2005, Mol Psychiatry. 2005.
18. Sullivan, E. V., Shear, P. K., et al., Cognitive and motor impairments are related to gray matter volume deficits in schizophrenia, Biol Psychiatry. 1996;39:234-40.
19. Lawrie, S. M. and Abukmeil, S. S., Brain abnormality in schizophrenia. A systematic and quantitative review of volumetric magnetic resonance imaging studies, Br J Psychiatry. 1998;172:110-20.
20. Thompson, P. M., Vidal, C., et al., Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia, Proc Natl Acad Sci U S A. 2001;98:11650-5.
21. Wilke, M., Kaufmann, C., et al., Gray matter-changes and correlates of disease severity in schizophrenia: a statistical parametric mapping study, Neuroimage. 2001;13:814-24.
22. Suzuki, M., Nohara, S., et al., Regional changes in brain gray and white matter in patients with schizophrenia demonstrated with voxel-based analysis of MRI, Schizophr Res. 2002;55:41-54.
23. Hulshoff Pol, H. E., Schnack, H. G., et al., Volume changes in gray matter in patients with schizophrenia, Am J Psychiatry. 2002;159:244-50.
24. Suddath, R. L., Christison, G. W., et al., Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia, N Engl J Med. 1990;322:789-94.
25. Gaser, C., Nenadic, I., et al., Ventricular enlargement in schizophrenia related to volume reduction of the thalamus, striatum, and superior temporal cortex, Am J Psychiatry. 2004;161:154-6.
26. Berman KF and DR., W., Functional localization in the brain in schizophrenia. In: Review of Psychiatry, vol. 10, Tasman A and Goldfinger S (eds), Washington DC: American Psychiatric Press, . 1991:pp. 24–59.
27. Snyder, S. H., The dopamine hypothesis of schizophrenia: focus on the dopamine receptor, Am J Psychiatry. 1976;133:197-202.
28. Abi-Dargham, A., Gil, R., et al., Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort, Am J Psychiatry. 1998;155:761-7.
29. Breier, A., Su, T. P., et al., Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method, Proc Natl Acad Sci U S A. 1997;94:2569-74.
30. Laruelle, M., Abi-Dargham, A., et al., Increased dopamine transmission in schizophrenia: relationship to illness phases, Biol Psychiatry. 1999;46:56-72.
31. Snyder, S. H., Amphetamine psychosis: a "model" schizophrenia mediated by catecholamines, Am J Psychiatry. 1973;130:61-7.
32. Creese, I., Burt, D. R., et al., Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs, Science. 1976;192:481-3.
33. Carlsson, A., The current status of the dopamine hypothesis of schizophrenia, Neuropsychopharmacology. 1988;1:179-86.
34. Balestrieri, A. and Fontanari, D., Acquired and crossed tolerance to mescaline, LSD-25, and BOL-148, Arch Gen Psychiatry. 1959;1:279-82.
35. Shaw, E. and Woolley, D. W., Some serotoninlike activities of lysergic acid diethylamide, Science. 1956;124:121-2.
36. 沈渔邨, 《精神病学(第三版)》, 北京,人民卫生出版社. 1994.
37. William M, S. P., Marggy GF, Noradrenergic function in schizophrenia, Arch Gen Psychiatry. 1987;44:898-914.
38. 金卫东,刘铁榜,臧德馨, 精神分裂症中枢神经介质假说的修正和发展, 中华神经精神科杂志. 1992;25:55-7.
39. Lucas-Meunier, E., Fossier, P., et al., Cholinergic modulation of the cortical neuronal network, Pflugers Arch. 2003;446:17-29.
40. 杜雨苍, 《神经肽与脑功能》, 上海, 上海科技教育出版社. 1998.
41. Botstein, D. and Risch, N., Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease, Nat Genet. 2003;33 Suppl:228-37.
42. Terwilliger, J. D. and Weiss, K. M., Linkage disequilibrium mapping of complex disease: fantasy or reality?, Curr Opin Biotechnol. 1998;9:578-94.
43. Cardon, L. R. and Bell, J. I., Association study designs for complex diseases, Nat Rev Genet. 2001;2:91-9.
44. Ott, J., Analysis of Human Genetic Linkage, The Johns Hopkins University Press. Third Edition.
45. Yang, X., She, C., et al., A locus for brachydactyly type A-1 maps to chromosome 2q35-q36, Am J Hum Genet. 2000;66:892-903.
46. Gao, B., Guo, J., et al., Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-1, Nat Genet. 2001;28:386-8.
47. Ardlie, K. G., Kruglyak, L., et al., Patterns of linkage disequilibrium in the human genome, Nat Rev Genet. 2002;3:299-309.
48. Pritchard, J. K. and Przeworski, M., Linkage disequilibrium in humans: models and data, Am J Hum Genet. 2001;69:1-14.
49. Sham, P., Statistics in Human Genetics, Arnold. 1998.
50. Terwilliger, J. D., Zollner, S., et al., Mapping genes through the use of linkage disequilibrium generated by genetic drift: 'drift mapping' in small populations with no demographic expansion, Hum Hered. 1998;48:138-54.
51. Cordell, H. J. and Clayton, D. G., Genetic association studies, Lancet. 2005;366:1121-31.
52. Risch, N. and Teng, J., The relative power of family-based and case-control designs for linkage disequilibrium studies of complex human diseases I. DNA pooling, Genome Res. 1998;8:1273-88.
53. Pritchard, J. K. and Rosenberg, N. A., Use of unlinked genetic markers to detect population stratification in association studies, Am J Hum Genet. 1999;65:220-8.
54. Devlin, B. and Roeder, K., Genomic control for association studies, Biometrics. 1999;55:997-1004.
55. Bacanu, S. A., Devlin, B., et al., The power of genomic control, Am J Hum Genet. 2000;66:1933-44.
56. Falk, C. T. and Rubinstein, P., Haplotype relative risks: an easy reliable way to construct a proper control sample for risk calculations, Ann Hum Genet. 1987;51 ( Pt 3):227-33.
57. Terwilliger, J. D. and Ott, J., A haplotype-based 'haplotype relative risk' approach to detecting allelic associations, Hum Hered. 1992;42:337-46.
58. Spielman, R. S., McGinnis, R. E., et al., Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM), Am J Hum Genet. 1993;52:506-16.
59. Ott, J., Statistical properties of the haplotype relative risk, Genet Epidemiol. 1989;6:127-30.
60. Reich, D. E. and Lander, E. S., On the allelic spectrum of human disease, Trends Genet. 2001;17:502-10.
61. Becker, K. G., The common variants/multiple disease hypothesis of common complex genetic disorders, Med Hypotheses. 2004;62:309-17.
62. Smith, D. J. and Lusis, A. J., The allelic structure of common disease, Hum Mol Genet. 2002;11:2455-61.
63. Morton, N. E., Linkage disequilibrium maps and association mapping, J Clin Invest. 2005;115:1425-30.
64. Bearden, C. E., Reus, V. I., et al., Why genetic investigation of psychiatric disorders is so difficult, Curr Opin Genet Dev. 2004;14:280-6.
65. Risch, N. and Merikangas, K., The future of genetic studies of complex human diseases, Science. 1996;273:1516-7.
66. Carlson, C. S., Eberle, M. A., et al., Mapping complex disease loci in whole-genome association studies, Nature. 2004;429:446-52.
67. Johnson, G. C., Esposito, L., et al., Haplotype tagging for the identification of common disease genes, Nat Genet. 2001;29:233-7.
68. Zhang, K., Qin, Z. S., et al., Haplotype block partitioning and tag SNP selection using genotype data and their applications to association studies, Genome Res. 2004;14:908-16.
69. Reich, D. E., Cargill, M., et al., Linkage disequilibrium in the human genome, Nature. 2001;411:199-204.
70. Daly, M. J., Rioux, J. D., et al., High-resolution haplotype structure in the human genome, Nat Genet. 2001;29:229-32.
71. Jeffreys, A. J., Kauppi, L., et al., Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex, Nat Genet. 2001;29:217-22.
72. van den Oord, E. J. and Neale, B. M., Will haplotype maps be useful for finding genes?, Mol Psychiatry. 2004;9:227-36.
73. Wall, J. D. and Pritchard, J. K., Haplotype blocks and linkage disequilibrium in the human genome, Nat Rev Genet. 2003;4:587-97.
74. Patil, N., Berno, A. J., et al., Blocks of limited haplotype diversity revealed by high-resolution scanning of human chromosome 21, Science. 2001;294:1719-23.
75. Zhang, K., Deng, M., et al., A dynamic programming algorithm for haplotype block partitioning, Proc Natl Acad Sci U S A. 2002;99:7335-9.
76. Zhang, K., Calabrese, P., et al., Haplotype block structure and its applications to associationstudies: power and study designs, Am J Hum Genet. 2002;71:1386-94.
77. Gabriel, S. B., Schaffner, S. F., et al., The structure of haplotype blocks in the human genome, Science. 2002;296:2225-9.
78. Kruglyak, L., Prospects for whole-genome linkage disequilibrium mapping of common disease genes, Nat Genet. 1999;22:139-44.
79. The International HapMap Project, Nature. 2003;426:789-96.
80. Integrating ethics and science in the International HapMap Project, Nat Rev Genet. 2004;5:467-75.
81. Altshuler, D., Brooks, L. D., et al., A haplotype map of the human genome, Nature. 2005;437:1299-320.
82. Sham, P. C. and Curtis, D., Monte Carlo tests for associations between disease and alleles at highly polymorphic loci, Ann Hum Genet. 1995;59 ( Pt 1):97-105.
83. Xie, X. and Ott, J., Testing linkage disequilibrium between a disease gene and marker loci, Am J Hum Genet. 1993;53:1107.
84. Zhao, J. H., Curtis, D., et al., Model-free analysis and permutation tests for allelic associations, Hum Hered. 2000;50:133-9.
85. Zhao, J. H. and Sham, P. C., Faster haplotype frequency estimation using unrelated subjects, Hum Hered. 2002;53:36-41.
86. Schneider, S., Roessli, D., et al., Arlequin: A software for population genetics data analysis. Ver 2.000, Genetics and Biometry Lab, Dept. of Anthropology, University of Geneva. 2000.
87. Stephens, M., Smith, N. J., et al., A new statistical method for haplotype reconstruction from population data, Am J Hum Genet. 2001;68:978-89.
88. Niu, T., Qin, Z. S., et al., Bayesian haplotype inference for multiple linked single-nucleotide polymorphisms, Am J Hum Genet. 2002;70:157-69.
89. Sham, P. C. and Curtis, D., An extended transmission/disequilibrium test (TDT) for multi-allele marker loci, Ann Hum Genet. 1995;59 ( Pt 3):323-36.
90. Clayton, D., A generalization of the transmission/disequilibrium test for uncertain-haplotype transmission, Am J Hum Genet. 1999;65:1170-7.
91. Horvath, S., Xu, X., et al., Family-based tests for associating haplotypes with general phenotype data: application to asthma genetics, Genet Epidemiol. 2004;26:61-9.
92. Laird, N. M., Horvath, S., et al., Implementing a unified approach to family-based tests of association, Genet Epidemiol. 2000;19 Suppl 1:S36-42.
93. Dudbridge, F., Pedigree disequilibrium tests for multilocus haplotypes, Genet Epidemiol. 2003;25:115-21.
94. Barrett, J. C., Fry, B., et al., Haploview: analysis and visualization of LD and haplotype maps, Bioinformatics. 2005;21:263-5.
95. Sklar, P., Linkage analysis in psychiatric disorders: the emerging picture, Annu Rev Genomics Hum Genet. 2002;3:371-413.
96. Mirnics, K., Middleton, F. A., et al., Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex, Neuron. 2000;28:53-67.
97. Larminie, C., Murdock, P., et al., Selective expression of regulators of G-protein signaling (RGS) in the human central nervous system, Brain Res Mol Brain Res. 2004;122:24-34.
98. Ross, E. M. and Wilkie, T. M., GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins, Annu Rev Biochem. 2000;69:795-827.
99. Chowdari, K. V., Mirnics, K., et al., Association and linkage analyses of RGS4 polymorphisms in schizophrenia, Hum Mol Genet. 2002;11:1373-80.
100. Fallin, M. D., Lasseter, V. K., et al., Bipolar I disorder and schizophrenia: a 440-single-nucleotide polymorphism screen of 64 candidate genes among Ashkenazi Jewish case-parent trios, Am J Hum Genet. 2005;77:918-36.
101. Chen, X., Dunham, C., et al., Regulator of G-protein signaling 4 (RGS4) gene is associated with schizophrenia in Irish high density families, Am J Med Genet. 2004;129B:23-6.
102. Zhang, F., St Clair, D., et al., Association analysis of the RGS4 gene in Han Chinese and Scottish populations with schizophrenia, Genes Brain Behav. 2005;4:444-8.
103. Sobell, J. L., Richard, C., et al., Failure to confirm association between RGS4 haplotypes and schizophrenia in Caucasians, Am J Med Genet B Neuropsychiatr Genet. 2005;139:23-7.
104. Millar, J. K., Wilson-Annan, J. C., et al., Disruption of two novel genes by a translocation co-segregating with schizophrenia, Hum Mol Genet. 2000;9:1415-23.
105. Ekelund, J., Hovatta, I., et al., Chromosome 1 loci in Finnish schizophrenia families, Hum Mol Genet. 2001;10:1611-7.
106. Hennah, W., Varilo, T., et al., Haplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects, Hum Mol Genet. 2003;12:3151-9.
107. Callicott, J. H., Straub, R. E., et al., Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia, Proc Natl Acad Sci U S A. 2005;102:8627-32.
108. Hodgkinson, C. A., Goldman, D., et al., Disrupted in Schizophrenia 1 (DISC1): Association with Schizophrenia, Schizoaffective Disorder, and Bipolar Disorder, Am J Hum Genet. 2004;75:862-72.
109. Sachs, N. A., Sawa, A., et al., A frameshift mutation in Disrupted in Schizophrenia 1 in an American family with schizophrenia and schizoaffective disorder, Mol Psychiatry. 2005;10:758-64.
110. Millar, J. K., Pickard, B. S., et al., DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling, Science. 2005;310:1187-91.
111. Kamiya, A., Kubo, K., et al., A schizophrenia-associated mutation of DISC1 perturbs cerebral cortex development, Nat Cell Biol. 2005;7:1167-78.
112. Sklar, P., Pato, M. T., et al., Genome-wide scan in Portuguese Island families identifies 5q31-5q35 as a susceptibility locus for schizophrenia and psychosis, Mol Psychiatry. 2004;9:213-8.
113. Petryshen, T. L., Middleton, F. A., et al., Genetic investigation of chromosome 5q GABA(A) receptor subunit genes in schizophrenia, Mol Psychiatry. 2005.
114. Roberts, E., Prospects for research on schizophrenia. An hypotheses suggesting that there is a defect in the GABA system in schizophrenia, Neurosci Res Program Bull. 1972;10:468-82.
115. Lewis, D. A., Hashimoto, T., et al., Cortical inhibitory neurons and schizophrenia, Nat Rev Neurosci. 2005;6:312-24.
116. Pimm, J., McQuillin, A., et al., The Epsin 4 gene on chromosome 5q, which encodes the clathrin-associated protein enthoprotin, is involved in the genetic susceptibility to schizophrenia, Am J Hum Genet. 2005;76:902-7.
117. Wasiak, S., Legendre-Guillemin, V., et al., Enthoprotin: a novel clathrin-associated protein identified through subcellular proteomics, J Cell Biol. 2002;158:855-62.
118. Straub, R. E., MacLean, C. J., et al., A potential vulnerability locus for schizophrenia on chromosome 6p24-22: evidence for genetic heterogeneity, Nat Genet. 1995;11:287-93.
119. Straub, R. E., Jiang, Y., et al., Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia, Am J Hum Genet. 2002;71:337-48.
120. Schwab, S. G., Knapp, M., et al., Support for association of schizophrenia with genetic variation in the 6p22.3 gene, dysbindin, in sib-pair families with linkage and in an additional sample of triad families, Am J Hum Genet. 2003;72:185-90.
121. Tang, J. X., Zhou, J., et al., Family-based association study of DTNBP1 in 6p22.3 and schizophrenia, Mol Psychiatry. 2003;8:717-8.
122. Kirov, G., Ivanov, D., et al., Strong evidence for association between the dystrobrevin binding protein 1 gene (DTNBP1) and schizophrenia in 488 parent-offspring trios from Bulgaria, Biol Psychiatry. 2004;55:971-5.
123. Hall, D., Gogos, J. A., et al., The contribution of three strong candidate schizophrenia susceptibility genes in demographically distinct populations, Genes Brain Behav. 2004;3:240-8.
124. De Luca, V., Voineskos, D., et al., Untranslated region haplotype in dysbindin gene: analysis in schizophrenia, J Neural Transm. 2005;112:1263-7.
125. Li, W., Zhang, Q., et al., Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1), Nat Genet. 2003;35:84-9.
126. Benson, M. A., Newey, S. E., et al., Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain, J Biol Chem. 2001;276:24232-41.
127. Talbot, K., Eidem, W. L., et al., Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia, J Clin Invest. 2004;113:1353-63.
128. Weickert, C. S., Straub, R. E., et al., Human dysbindin (DTNBP1) gene expression in normal brain and in schizophrenic prefrontal cortex and midbrain, Arch Gen Psychiatry. 2004;61:544-55.
129. Numakawa, T., Yagasaki, Y., et al., Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia, Hum Mol Genet. 2004;13:2699-708.
130. Levinson, D. F., Holmans, P., et al., Multicenter linkage study of schizophrenia candidate regions on chromosomes 5q, 6q, 10p, and 13q: schizophrenia linkage collaborative group III, Am J Hum Genet. 2000;67:652-63.
131. Duan, J., Martinez, M., et al., Polymorphisms in the trace amine receptor 4 (TRAR4) gene on chromosome 6q23.2 are associated with susceptibility to schizophrenia, Am J Hum Genet. 2004;75:624-38.
132. Duan, S., Du, J., et al., Failure to find association between TRAR4 and schizophrenia in the Chinese Han population, J Neural Transm. 2005.
133. Ikeda, M., Iwata, N., et al., No association of haplotype-tagging SNPs in TRAR4 with schizophrenia in Japanese patients, Schizophr Res. 2005;78:127-30.
134. Borowsky, B., Adham, N., et al., Trace amines: identification of a family of mammalian G protein-coupled receptors, Proc Natl Acad Sci U S A. 2001;98:8966-71.
135. Abou Jamra, R., Sircar, I., et al., A family-based and case-control association study of trace amine receptor genes on chromosome 6q23 in bipolar affective disorder, Mol Psychiatry. 2005;10:618-20.
136. Marti, S. B., Cichon, S., et al., Metabotropic glutamate receptor 3 (GRM3) gene variation is not associated with schizophrenia or bipolar affective disorder in the German population, Am J Med Genet. 2002;114:46-50.
137. Fujii, Y., Shibata, H., et al., Positive associations of polymorphisms in the metabotropic glutamate receptor type 3 gene (GRM3) with schizophrenia, Psychiatr Genet. 2003;13:71-6.
138. Egan, M. F., Straub, R. E., et al., Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia, Proc Natl Acad Sci U S A. 2004;101:12604-9.
139. Chen, Q., He, G., et al., A case-control study of the relationship between the metabotropic glutamate receptor 3 gene and schizophrenia in the Chinese population, Schizophr Res. 2005;73:21-6.
140. Norton, N., Williams, H. J., et al., No evidence for association between polymorphisms in GRM3 and schizophrenia, BMC Psychiatry. 2005;5:23.
141. Gerber, D. J., Hall, D., et al., Evidence for association of schizophrenia with genetic variation in the 8p21.3 gene, PPP3CC, encoding the calcineurin gamma subunit, Proc Natl Acad Sci U S A. 2003;100:8993-8.
142. Eastwood, S. L., Burnet, P. W., et al., Decreased hippocampal expression of the susceptibility gene PPP3CC and other calcineurin subunits in schizophrenia, Biol Psychiatry. 2005;57:702-10.
143. Miyakawa, T., Leiter, L. M., et al., Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia, Proc Natl Acad Sci U S A. 2003;100:8987-92.
144. Corfas, G., Roy, K., et al., Neuregulin 1-erbB signaling and the molecular/cellular basis of schizophrenia, Nat Neurosci. 2004;7:575-80.
145. Stefansson, H., Sigurdsson, E., et al., Neuregulin 1 and susceptibility to schizophrenia, Am J Hum Genet. 2002;71:877-92.
146. Stefansson, H., Sarginson, J., et al., Association of neuregulin 1 with schizophrenia confirmed in a Scottish population, Am J Hum Genet. 2003;72:83-7.
147. Yang, J. Z., Si, T. M., et al., Association study of neuregulin 1 gene with schizophrenia, Mol Psychiatry. 2003;8:706-9.
148. Zhao, X., Shi, Y., et al., A case control and family based association study of the neuregulin1 gene and schizophrenia, J Med Genet. 2004;41:31-4.
149. Li, T., Stefansson, H., et al., Identification of a novel neuregulin 1 at-risk haplotype in Han schizophrenia Chinese patients, but no association with the Icelandic/Scottish risk haplotype, Mol Psychiatry. 2004;9:698-704.
150. Thiselton, D. L., Webb, B. T., et al., No evidence for linkage or association of neuregulin-1 (NRG1) with disease in the Irish study of high-density schizophrenia families (ISHDSF), Mol Psychiatry. 2004;9:729.
151. Duan, J., Martinez, M., et al., Neuregulin 1 ( NRG1 ) and schizophrenia: analysis of a US family sample and the evidence in the balance, Psychol Med. 2005;35:1599-610.
152. Badner, J. A. and Gershon, E. S., Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia, Mol Psychiatry. 2002;7:405-11.
153. Detera-Wadleigh, S. D., Badner, J. A., et al., A high-density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2, Proc Natl Acad Sci U S A. 1999;96:5604-9.
154. Chumakov, I., Blumenfeld, M., et al., Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia, Proc Natl Acad Sci U S A. 2002;99:13675-80.
155. Mothet, J. P., Parent, A. T., et al., D-serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor, Proc Natl Acad Sci U S A. 2000;97:4926-31.
156. Hattori, E., Liu, C., et al., Polymorphisms at the G72/G30 gene locus, on 13q33, are associated with bipolar disorder in two independent pedigree series, Am J Hum Genet. 2003;72:1131-40.
157. Schumacher, J., Jamra, R. A., et al., Examination of G72 and D-amino-acid oxidase as genetic risk factors for schizophrenia and bipolar affective disorder, Mol Psychiatry. 2004;9:203-7.
158. Wang, X., He, G., et al., Association of G72/G30 with schizophrenia in the Chinese population, Biochem Biophys Res Commun. 2004;319:1281-6.
159. Addington, A. M., Gornick, M., et al., Polymorphisms in the 13q33.2 gene G72/G30 are associated with childhood-onset schizophrenia and psychosis not otherwise specified, Biol Psychiatry. 2004;55:976-80.
160. Korostishevsky, M., Kaganovich, M., et al., Is the G72/G30 locus associated with schizophrenia? single nucleotide polymorphisms, haplotypes, and gene expression analysis, Biol Psychiatry. 2004;56:169-76.
161. Korostishevsky, M., Kremer, I., et al., Transmission disequilibrium and haplotype analyses of the G72/G30 locus: Suggestive linkage to schizophrenia in Palestinian Arabs living in the North ofIsrael, Am J Med Genet B Neuropsychiatr Genet. 2005.
162. Mulle, J. G., Chowdari, K. V., et al., No evidence for association to the G72/G30 locus in an independent sample of schizophrenia families, Mol Psychiatry. 2005;10:431-3.
163. Zou, F., Li, C., et al., A family-based study of the association between the G72/G30 genes and schizophrenia in the Chinese population, Schizophr Res. 2005;73:257-61.
164. Emamian, E. S., Hall, D., et al., Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia, Nat Genet. 2004;36:131-7.
165. Ohtsuki, T., Inada, T., et al., Failure to confirm association between AKT1 haplotype and schizophrenia in a Japanese case-control population, Mol Psychiatry. 2004;9:981-3.
166. Ikeda, M., Iwata, N., et al., Positive association of AKT1 haplotype to Japanese methamphetamine use disorder, Int J Neuropsychopharmacol. 2005:1-5.
167. Schwab, S. G., Hoefgen, B., et al., Further evidence for association of variants in the AKT1 gene with schizophrenia in a sample of European sib-pair families, Biol Psychiatry. 2005;58:446-50.
168. Lewis, C. M., Levinson, D. F., et al., Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia, Am J Hum Genet. 2003;73:34-48.
169. Karayiorgou, M., Morris, M. A., et al., Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11, Proc Natl Acad Sci U S A. 1995;92:7612-6.
170. Pulver, A. E., Nestadt, G., et al., Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives, J Nerv Ment Dis. 1994;182:476-8.
171. Murphy, K. C., Jones, L. A., et al., High rates of schizophrenia in adults with velo-cardio-facial syndrome, Arch Gen Psychiatry. 1999;56:940-5.
172. Liu, H., Heath, S. C., et al., Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia, Proc Natl Acad Sci U S A. 2002;99:3717-22.
173. Liu, H., Abecasis, G. R., et al., Genetic variation in the 22q11 locus and susceptibility to schizophrenia, Proc Natl Acad Sci U S A. 2002;99:16859-64.
174. Li, T., Ma, X., et al., Evidence for association between novel polymorphisms in the PRODH gene and schizophrenia in a Chinese population, Am J Med Genet. 2004;129B:13-5.
175. Williams, H. J., Williams, N., et al., Association between PRODH and schizophrenia is not confirmed, Mol Psychiatry. 2003;8:644-5.
176. Gothelf, D., Eliez, S., et al., COMT genotype predicts longitudinal cognitive decline and psychosis in 22q11.2 deletion syndrome, Nat Neurosci. 2005;8:1500-2.
177. Jacquet, H., Raux, G., et al., PRODH mutations and hyperprolinemia in a subset of schizophrenic patients, Hum Mol Genet. 2002;11:2243-9.
178. Jacquet, H., Demily, C., et al., Hyperprolinemia is a risk factor for schizoaffective disorder, Mol Psychiatry. 2005;10:479-85.
179. Bender, H. U., Almashanu, S., et al., Functional consequences of PRODH missense mutations, Am J Hum Genet. 2005;76:409-20.
180. Paterlini, M., Zakharenko, S. S., et al., Transcriptional and behavioral interaction between 22q11.2 orthologs modulates schizophrenia-related phenotypes in mice, Nat Neurosci. 2005;8:1586-94.
181. Weinshilboum, R. M., Otterness, D. M., et al., Methylation pharmacogenetics: catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase, Annu Rev Pharmacol Toxicol. 1999;39:19-52.
182. Lotta, T., Vidgren, J., et al., Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme, Biochemistry. 1995;34:4202-10.
183. Lachman, H. M., Papolos, D. F., et al., Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders, Pharmacogenetics. 1996;6:243-50.
184. Palmatier, M. A., Kang, A. M., et al., Global variation in the frequencies of functionally different catechol-O-methyltransferase alleles, Biol Psychiatry. 1999;46:557-67.
185. DeMille, M. M., Kidd, J. R., et al., Population variation in linkage disequilibrium across the COMT gene considering promoter region and coding region variation, Hum Genet. 2002;111:521-37.
186. Li, T., Sham, P. C., et al., Preferential transmission of the high activity allele of COMT in schizophrenia, Psychiatr Genet. 1996;6:131-3.
187. Li, T., Ball, D., et al., Family-based linkage disequilibrium mapping using SNP marker haplotypes: application to a potential locus for schizophrenia at chromosome 22q11, Mol Psychiatry. 2000;5:452.
188. Chen, X., Wang, X., et al., Variants in the catechol-o-methyltransferase (COMT) gene are associated with schizophrenia in Irish high-density families, Mol Psychiatry. 2004;9:962-7.
189. Egan, M. F., Goldberg, T. E., et al., Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia, Proc Natl Acad Sci U S A. 2001;98:6917-22.
190. Harrison, P. J. and Weinberger, D. R., Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence, Mol Psychiatry. 2004.
191. Chen, J., Lipska, B. K., et al., Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain, Am J Hum Genet. 2004;75:807-21.
192. Shifman, S., Bronstein, M., et al., A highly significant association between a COMT haplotype and schizophrenia, Am J Hum Genet. 2002;71:1296-302.
193. Mukai, J., Liu, H., et al., Evidence that the gene encoding ZDHHC8 contributes to the risk of schizophrenia, Nat Genet. 2004;36:725-31.
194. Chen, W. Y., Shi, Y. Y., et al., Case-control study and transmission disequilibrium test provide consistent evidence for association between schizophrenia and genetic variation in the 22q11 gene ZDHHC8, Hum Mol Genet. 2004;13:2991-5.
195. Glaser, B., Schumacher, J., et al., No association between the putative functional ZDHHC8 single nucleotide polymorphism rs175174 and schizophrenia in large European samples, Biol Psychiatry. 2005;58:78-80.
196. Addington, A. M., Gornick, M., et al., GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD(67)), is associated with childhood-onset schizophrenia and cortical gray matter volume loss, Mol Psychiatry. 2004.
197. Chen, Q., He, G., et al., Positive association between synapsin II and schizophrenia, Biol Psychiatry. 2004;56:177-81.
198. Chen, Q., He, G., et al., Family-Based Association Study of Synapsin II and Schizophrenia, Am J Hum Genet. 2004;75:873-7.
199. Neves-Pereira, M., Cheung, J. K., et al., BDNF gene is a risk factor for schizophrenia in a Scottish population, Mol Psychiatry. 2005;10:208-12.
200. Schumacher, J., Jamra, R. A., et al., Evidence for a relationship between genetic variants at the brain-derived neurotrophic factor (BDNF) locus and major depression, Biol Psychiatry. 2005;58:307-14.
201. Freedman, R., Adams, C. E., et al., The alpha7-nicotinic acetylcholine receptor and the pathology of hippocampal interneurons in schizophrenia, J Chem Neuroanat. 2000;20:299-306.
202. Leonard, S., Gault, J., et al., Association of promoter variants in the alpha7 nicotinic acetylcholine receptor subunit gene with an inhibitory deficit found in schizophrenia, Arch Gen Psychiatry. 2002;59:1085-96.
203. Sakowicz, R., Berdelis, M. S., et al., A marine natural product inhibitor of kinesin motors, Science. 1998;280:292-5.
204. Stewart, R. J., Thaler, J. P., et al., Direction of microtubule movement is an intrinsic property of the motor domains of kinesin heavy chain and Drosophila ncd protein, Proc Natl Acad Sci U S A. 1993;90:5209-13.
205. Goodson, H. V., Kang, S. J., et al., Molecular phylogeny of the kinesin family of microtubule motor proteins, J Cell Sci. 1994;107 ( Pt 7):1875-84.
206. VALE RD and RJ, F., The design plan of kinesin motors, Ann Rev Cell Dev Biol. 1977;13:745-77.
207. Hirokawa, N., Kinesin and dynein superfamily proteins and the mechanism of organelle transport, Science. 1998;279:519-26.
208. Lawrence, C. J., Dawe, R. K., et al., A standardized kinesin nomenclature, J Cell Biol. 2004;167:19-22.
209. Schnapp, B. J., Reese, T. S., et al., Kinesin is bound with high affinity to squid axon organelles that move to the plus-end of microtubules, J Cell Biol. 1992;119:389-99.
210. Hirose, K. and Amos, L. A., Three-dimensional structure of motor molecules, Cell Mol Life Sci. 1999;56:184-99.
211. Kull, F. J., Motor proteins of the kinesin superfamily: structure and mechanism. in Essays inBiochemistry.Molecular Motors edited Banting G, Higgins S.J., Portland Press. 2000;,London 61-73.
212. Howard, J., Molecular motors: structural adaptations to cellular functions, Nature. 1997;389:561-7.
213. Verhey, K. J., Lizotte, D. L., et al., Light chain-dependent regulation of Kinesin's interaction with microtubules, J Cell Biol. 1998;143:1053-66.
214. Weinberger, D. R., Berman, K. F., et al., Evidence of dysfunction of a prefrontal-limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins, Am J Psychiatry. 1992;149:890-7.
215. Csernansky, J. G., Wang, L., et al., Hippocampal deformities in schizophrenia characterized by high dimensional brain mapping, Am J Psychiatry. 2002;159:2000-6.
216. Kamiya, A., Tomoda, T., et al., DISC1-NDEL1/NUDEL protein interaction, an essential component for neurite outgrowth, is modulated by genetic variations of DISC1, Hum Mol Genet. 2006;15:3313-23.
217. Aizawa, H., Sekine, Y., et al., Kinesin family in murine central nervous system, J Cell Biol. 1992;119:1287-96.
218. American Psychiatric Association Diagnostic and statistical manual of mental disorders, DSM-Ⅲ-R, 3d ed, rev, Washington, DC. American Psychiatric Press. 1987.
219. Germer, S., Holland, M. J., et al., High-throughput SNP allele-frequency determination in pooled DNA samples by kinetic PCR, Genome Res. 2000;10:258-66.
220. Ye, S., Dhillon, S., et al., An efficient procedure for genotyping single nucleotide polymorphisms, Nucleic Acids Res. 2001;29:E88-8.
221. Zapata, C., Carollo, C., et al., Sampling variance and distribution of the D' measure of overall gametic disequilibrium between multiallelic loci, Ann Hum Genet. 2001;65:395-406.
222. Rabinowitz, D. and Laird, N., A unified approach to adjusting association tests for population admixture with arbitrary pedigree structure and arbitrary missing marker information, Hum Hered. 2000;50:211-23.
223. Barrett JC, Fry B, et al., Haploview: analysis and visualization of LD and haplotype maps, Bioinformatics. 2005;Jan.
224. Detera-Wadleigh, S. D., Goldin, L. R., et al., Exclusion of linkage to 5q11-13 in families with schizophrenia and other psychiatric disorders, Nature. 1989;340:391-3.
225. Mayor, C., Brudno, M., et al., VISTA : visualizing global DNA sequence alignments of arbitrary length, Bioinformatics. 2000;16:1046-7.
226. Schwartz, S., Elnitski, L., et al., MultiPipMaker and supporting tools: Alignments and analysis of multiple genomic DNA sequences, Nucleic Acids Res. 2003;31:3518-24.
227. Carter, K. W. and McCaskie, P. A., Linkage disequilibrium and haplotyping: applications to genetic epidemiology (Presentation, May 10th, 2005), Population Health Seminar Series, School of Population Health, The University of Western Australia. 2005.
228. Levinson, D. F., Mahtani, M. M., et al., Genome scan of schizophrenia, Am J Psychiatry. 1998;155:741-50.
229. Mowry, B. J., Ewen, K. R., et al., Second stage of a genome scan of schizophrenia: study of five positive regions in an expanded sample, Am J Med Genet. 2000;96:864-9.
230. Paunio, T., Tuulio-Henriksson, A., et al., Search for cognitive trait components of schizophrenia reveals a locus for verbal learning and memory on 4q and for visual working memory on 2q, Hum Mol Genet. 2004;13:1693-702.
231. Maeno-Hikichi, Y., Chang, S., et al., A PKC epsilon-ENH-channel complex specifically modulates N-type Ca2+ channels, Nat Neurosci. 2003;6:468-75.
232. Wu, M., Li, Y., et al., Cloning and identification of a novel human gene PDLIM5, a homolog of AD-associated neuronal thread protein (AD7c-NTP), DNA Seq. 2004;15:144-7.
233. Iwamoto, K., Kakiuchi, C., et al., Molecular characterization of bipolar disorder by comparing gene expression profiles of postmortem brains of major mental disorders, Mol Psychiatry. 2004;9:406-16.
234. Iwamoto, K., Bundo, M., et al., Expression of HSPF1 and LIM in the lymphoblastoid cells derived from patients with bipolar disorder and schizophrenia, J Hum Genet. 2004;49:227-31.
235. Kato, T., Iwayama, Y., et al., Gene expression and association analyses of LIM (PDLIM5) in bipolar disorder and schizophrenia, Mol Psychiatry. 2005;10:1045-55.
236. Horiuchi, Y., Arai, M., et al., A polymorphism in the PDLIM5 gene associated with gene expression and schizophrenia, Biol Psychiatry. 2006;59:434-9.
237. Sham, P. C. and Curtis, D., Monte Carlo tests for associations between disease and alleles at highly polymorphic loci, Ann Hum Genet. 1995;59:97-105.
238. Cordell, H. J. and Clayton, D. G., A unified stepwise regression procedure for evaluating the relative effects of polymorphisms within a gene using case/control or family data: application to HLA in type 1 diabetes, Am J Hum Genet. 2002;70:124-41.
239. Mander, A., Haplotype analysis in population-based association studies., STATA J. 2001;1:58-75.
240. Erdfelder, E., Faul, F., et al., G*Power: a general power analysis grogram, Behav Res Methods Instrum Comput. 1996;28:1-11.
241. Iga, J., Ueno, S., et al., Gene expression and association analysis of LIM (PDLIM5) in major depression, Neurosci Lett. 2006;400:203-7.
242. Risch, N., Burchard, E., et al., Categorization of humans in biomedical research: genes, race and disease, Genome Biol. 2002;3:comment2007.
243. Schulz, T. W., Nakagawa, T., et al., Actin/alpha-actinin-dependent transport of AMPA receptors in dendritic spines: role of the PDZ-LIM protein RIL, J Neurosci. 2004;24:8584-94.