Association between common alcohol dehydrogenase gene (ADH) variants and schizophrenia and autism

详细信息    查看全文

• 作者：Lingjun Zuo (1)
  Kesheng Wang (2)
  Xiang-Yang Zhang (3)
  Xinghua Pan (4)
  Guilin Wang (5)
  Yunlong Tan (6)
  Chunlong Zhong (7)
  John H. Krystal (1)
  Matthew State (1)
  Heping Zhang (8)
  Xingguang Luo (1)
  
• 刊名：Human Genetics
• 出版年：2013
• 出版时间：July 2013
• 年：2013
• 卷：132
• 期：7
• 页码：735-743
• 全文大小：271KB
• 参考文献：1. Abi-Dargham A, Laruelle M, Aghajanian GK, Charney D, Krystal J (1997) The role of serotonin in the pathophysiology and treatment of schizophrenia. J Neuropsychiatry Clin Neurosci 9:1-7
  2. Adamsen D, Meili D, Blau N, Thony B, Ramaekers V (2011) Autism associated with low 5-hydroxyindoleace acid in CSF and the heterozygous SLC6A4 gene Gly56Ala plus 5-HTTLPR L/L promoter variants. Mol Genet Metab 102:368-73 CrossRef
  3. AGP: The AGP Consortium (2007) Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet 39(3):319-28
  4. AGP: The AGP Consortium (2010) Functional impact of global rare copy number variation in autism spectrum disorders. Nature 466(7204):368-72
  5. AGP: The AGP Consortium (2010) A genome-wide scan for common alleles affecting risk for autism. Hum Mol Genet 19(20):4072-082
  6. American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Press, Washington DC
  7. Anney R, Klei L, Pinto D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Sykes N, Pagnamenta AT, Almeida J, Bacchelli E, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bolte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Carson AR, Casallo G, Casey J, Chu SH, Cochrane L, Corsello C, Crawford EL, Crossett A, Dawson G, de Jonge M, Delorme R, Drmic I, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Goldberg J, Green J, Guter SJ, Hakonarson H, Heron EA, Hill M, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Korvatska O, Kustanovich V, Lajonchere CM, Lamb JA, Laskawiec M, Leboyer M, Le Couteur A, Leventhal BL, Lionel AC, Liu XQ, Lord C, Lotspeich L, Lund SC, Maestrini E, Mahoney W, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Melhem NM, Merikangas A, Migita O, Minshew NJ, Mirza GK, Munson J, Nelson SF, Noakes C, Noor A, Nygren G, Oliveira G, Papanikolaou K, Parr JR, Parrini B, Paton T, Pickles A, Piven J, Posey DJ, Poustka A, Poustka F, Prasad A, Ragoussis J, Renshaw K, Rickaby J, Roberts W, Roeder K, Roge B, Rutter ML, Bierut LJ, Rice JP, Salt J, Sansom K, Sato D, Segurado R, Senman L, Shah N, Sheffield VC, Soorya L, Sousa I, Stoppioni V, Strawbridge C, Tancredi R, Tansey K, Thiruvahindrapduram B, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Wallace S, Wang K, Wang Z, Wassink TH, Wing K, Wittemeyer K, Wood S, Yaspan BL, Zurawiecki D, Zwaigenbaum L, Betancur C, Buxbaum JD, Cantor RM, Cook EH, Coon H, Cuccaro ML, Gallagher L, Geschwind DH, Gill M, Haines JL, Miller J, Monaco AP, Nurnberger JI Jr, Paterson AD, Pericak-Vance MA, Schellenberg GD, Scherer SW, Sutcliffe JS, Szatmari P, Vicente AM, Vieland VJ, Wijsman EM, Devlin B, Ennis S, Hallmayer J (2010) A genome-wide scan for common alleles affecting risk for autism. Hum Mol Genet 19:4072-082 CrossRef
  8. Browning BL, Browning SR (2009) A unified approach to genotype imputation and haplotype-phase inference for large data sets of trios and unrelated individuals. Am J Hum Genet 84:210-23 CrossRef
  9. Buervenich S, Sydow O, Carmine A, Zhang Z, Anvret M, Olson L (2000) Alcohol dehydrogenase alleles in Parkinson’s disease. Mov Disord 15:813-18 CrossRef
  10. Chugani DC (2004) Serotonin in autism and pediatric epilepsies. Ment Retard Dev Disabil Res Rev 10:112-16 CrossRef
  11. Cook EH, Leventhal BL (1996) The serotonin system in autism. Curr Opin Pediatr 8:348-54 CrossRef
  12. Dickson SP, Wang K, Krantz I, Hakonarson H, Goldstein DB (2010) Rare variants create synthetic genome-wide associations. PLoS Biol 8:e1000294 CrossRef
  13. Filippini N, Rao A, Wetten S, Gibson RA, Borrie M, Guzman D, Kertesz A, Loy-English I, Williams J, Nichols T, Whitcher B, Matthews PM (2009) Anatomically-distinct genetic associations of APOE epsilon4 allele load with regional cortical atrophy in Alzheimer's disease. Neuroimage 44(3):724-28
  14. Frank J, Cichon S, Treutlein J, Ridinger M, Mattheisen M, Hoffmann P, Herms S, Wodarz N, Soyka M, Zill P, Maier W, Mossner R, Gaebel W, Dahmen N, Scherbaum N, Schmal C, Steffens M, Lucae S, Ising M, Muller-Myhsok B, Nothen MM, Mann K, Kiefer F, Rietschel M (2012) Genome-wide significant association between alcohol dependence and a variant in the ADH gene cluster. Addict Biol 17:171-80 CrossRef
  15. Holmes RS (1994) Alcohol dehydrogenases: a family of isozymes with differential functions. Alcohol Alcohol Suppl 2:127-30
  16. Howie BN, Donnelly P, Marchini J (2009) A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet 5:e1000529 CrossRef
  17. Leboyer M, Bouvard MP, Launay JM, Tabuteau F, Waller D, Dugas M, Kerdelhue B, Lensing P, Panksepp J (1992) Brief report: a double-blind study of naltrexone in infantile autism. J Autism Dev Disord 22:309-19 CrossRef
  18. Li J, Ji L (2005) Adjusting multiple testing in multilocus analyses using the eigenvalues of a correlation matrix. Heredity 95:221-27 CrossRef
  19. Li H, Wetten S, Li L, St Jean PL, Upmanyu R, Surh L, Hosford D, Barnes MR, Briley JD, Borrie M, Coletta N, Delisle R, Dhalla D, Ehm MG, Feldman HH, Fornazzari L, Gauthier S, Goodgame N, Guzman D, Hammond S, Hollingworth P, Hsiung GY, Johnson J, Kelly DD, Keren R, Kertesz A, King KS, Lovestone S, Loy-English I, Matthews PM, Owen MJ, Plumpton M, Pryse-Phillips W, Prinjha RK, Richardson JC, Saunders A, Slater AJ, St George-Hyslop PH, Stinnett SW, Swartz JE, Taylor RL, Wherrett J, Williams J, Yarnall DP, Gibson RA, Irizarry MC, Middleton LT, Roses AD (2008) Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease. Arch Neurol 65(1):45-3
  20. Luo X, Kranzler HR, Zuo L, Wang S, Schork NJ, Gelernter J (2006) Diplotype trend regression analysis of the ADH gene cluster and the ALDH2 gene: multiple significant associations with alcohol dependence. Am J Hum Genet 78:973-87 CrossRef
  21. Luo X, Kranzler HR, Zuo L, Zhang H, Wang S, Gelernter J (2008) ADH7 variation modulates extraversion and conscientiousness in substance-dependent subjects. Am J Med Genet B Neuropsychiatr Genet 147B:179-86 CrossRef
  22. McCarthy SE, Makarov V, Kirov G, Addington AM, McClellan J, Yoon S, Perkins DO, Dickel DE, Kusenda M, Krastoshevsky O, Krause V, Kumar RA, Grozeva D, Malhotra D, Walsh T, Zackai EH, Kaplan P, Ganesh J, Krantz ID, Spinner NB, Roccanova P, Bhandari A, Pavon K, Lakshmi B, Leotta A, Kendall J, Lee YH, Vacic V, Gary S, Iakoucheva LM, Crow TJ, Christian SL, Lieberman JA, Stroup TS, Lehtimaki T, Puura K, Haldeman-Englert C, Pearl J, Goodell M, Willour VL, Derosse P, Steele J, Kassem L, Wolff J, Chitkara N, McMahon FJ, Malhotra AK, Potash JB, Schulze TG, Nothen MM, Cichon S, Rietschel M, Leibenluft E, Kustanovich V, Lajonchere CM, Sutcliffe JS, Skuse D, Gill M, Gallagher L, Mendell NR, Craddock N, Owen MJ, O’Donovan MC, Shaikh TH, Susser E, Delisi LE, Sullivan PF, Deutsch CK, Rapoport J, Levy DL, King MC, Sebat J (2009) Microduplications of 16p11.2 are associated with schizophrenia. Nat Genet 41:1223-227 CrossRef
  23. Owen MJ, O’Donovan MC, Thapar A, Craddock N (2011) Neurodevelopmental hypothesis of schizophrenia. Br J Psychiatry 198:173-75 CrossRef
  24. Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155:945-59
  25. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559-75 CrossRef
  26. Sebat J, Levy DL, McCarthy SE (2009) Rare structural variants in schizophrenia: one disorder, multiple mutations; one mutation, multiple disorders. Trends Genet 25:528-35 CrossRef
  27. Stefansson H, Ophoff RA, Steinberg S, Andreassen OA, Cichon S, Rujescu D, Werge T, Pietilainen OP, Mors O, Mortensen PB, Sigurdsson E, Gustafsson O, Nyegaard M, Tuulio-Henriksson A, Ingason A, Hansen T, Suvisaari J, Lonnqvist J, Paunio T, Borglum AD, Hartmann A, Fink-Jensen A, Nordentoft M, Hougaard D, Norgaard-Pedersen B, Bottcher Y, Olesen J, Breuer R, Moller HJ, Giegling I, Rasmussen HB, Timm S, Mattheisen M, Bitter I, Rethelyi JM, Magnusdottir BB, Sigmundsson T, Olason P, Masson G, Gulcher JR, Haraldsson M, Fossdal R, Thorgeirsson TE, Thorsteinsdottir U, Ruggeri M, Tosato S, Franke B, Strengman E, Kiemeney LA, Melle I, Djurovic S, Abramova L, Kaleda V, Sanjuan J, de Frutos R, Bramon E, Vassos E, Fraser G, Ettinger U, Picchioni M, Walker N, Toulopoulou T, Need AC, Ge D, Yoon JL, Shianna KV, Freimer NB, Cantor RM, Murray R, Kong A, Golimbet V, Carracedo A, Arango C, Costas J, Jonsson EG, Terenius L, Agartz I, Petursson H, Nothen MM, Rietschel M, Matthews PM, Muglia P, Peltonen L, St Clair D, Goldstein DB, Stefansson K, Collier DA (2009) Common variants conferring risk of schizophrenia. Nature 460:744-47
  28. Storey JD, Tibshirani R (2003) Statistical significance for genomewide studies. Proc Natl Acad Sci USA 100:9440-445 CrossRef
  29. Svensson S, Some M, Lundsjo A, Helander A, Cronholm T, Hoog JO (1999) Activities of human alcohol dehydrogenases in the metabolic pathways of ethanol and serotonin. Eur J Biochem/FEBS 262:324-29 CrossRef
  30. Thomasson HR, Beard JD, Li TK (1995) ADH2 gene polymorphisms are determinants of alcohol pharmacokinetics. Alcohol Clin Exp Res 19:1494-499 CrossRef
  31. Wieselgren IM, Lindstrom LH (1998) CSF levels of HVA and 5-HIAA in drug-free schizophrenic patients and healthy controls: a prospective study focused on their predictive value for outcome in schizophrenia. Psychiatry Res 81:101-10 CrossRef
  32. Yoshida A, Rzhetsky A, Hsu LC, Chang C (1998) Human aldehyde dehydrogenase gene family. Eur J Biochem/FEBS 251:549-57 CrossRef
  33. Zuo L, Gelernter J, Kranzler HR, Stein MB, Zhang H, Wei F, Sen S, Poling J, Luo X (2009) ADH1A variation predisposes to personality traits and substance dependence. Am J Med Genet B Neuropsychiatr Genet 153B:376-86
  34. Zuo L, Zhang CK, Wang F, Li CS, Zhao H, Lu L, Zhang XY, Lu L, Zhang H, Zhang F, Krystal JH, Luo X (2011) A novel, functional and replicable risk gene region for alcohol dependence identified by genome-wide association study. PLoS One 6:e26726 CrossRef
  35. Zuo L, Gelernter J, Zhang CK, Zhao H, Lu L, Kranzler HR, Malison RT, Li CR, Wang F, Zhang XY, Deng HW, Krystal JH, Zhang F, Luo X (2012) Genome-wide association study of alcohol dependence implicates KIAA0040 on chromosome 1q. Neuropsychopharmacology 37:557-66 CrossRef
  36. Zuo L, Wang F, Zhang XY, Li CSR, Lu L, Ye L, Zhang H, Krystal JH, Deng HW, Luo X (2013a) Genome-wide significant association signals in IPO11-HTR1A region specific for alcohol and nicotine co-dependence. Alcohol Clin Exp Res. doi:10.1111/acer.12032
  37. Zuo L, Zhang H, Malison RT, Li CSR, Zhang XY, Wang F, Lu L, Lu L, Wang X, Krystal JH, Zhang F, Deng H, Luo X (2013b) Rare ADH variant constellations are specific for alcohol dependence. Alcohol Alcohol 48:9-4 (Oxford, Oxfordshire) CrossRef
  
• 作者单位：Lingjun Zuo (1)
  Kesheng Wang (2)
  Xiang-Yang Zhang (3)
  Xinghua Pan (4)
  Guilin Wang (5)
  Yunlong Tan (6)
  Chunlong Zhong (7)
  John H. Krystal (1)
  Matthew State (1)
  Heping Zhang (8)
  Xingguang Luo (1)
  
  1. Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06516, USA
  2. Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, TN, USA
  3. Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA
  4. Department of Genetics, Yale University School of Medicine, New Haven, CT, USA
  5. Yale Center for Genome Analysis, Yale University School of Medicine, Orange, CT, USA
  6. Biological Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing, China
  7. Department of Neurology, Renji Hospital, Shanghai Jiaotong University, Shanghai, China
  8. Department of Biostatistics, Yale University School of Epidemiology and Public Health, New Haven, CT, USA
  
• ISSN：1432-1203

文摘

Humans express at least seven alcohol dehydrogenase (ADH) isoforms that are encoded by ADH gene cluster (ADH7-em class="a-plus-plus">ADH1C-em class="a-plus-plus">ADH1B-em class="a-plus-plus">ADH1A-em class="a-plus-plus">ADH6-em class="a-plus-plus">ADH4-em class="a-plus-plus">ADH5) at chromosome 4. ADHs are key catabolic enzymes for retinol and ethanol. The functional ADH variants (mostly rare) have been implicated in alcoholism risk. In addition to catalyzing the oxidation of retinol and ethanol, ADHs may be involved in the metabolic pathways of several neurotransmitters that are implicated in the neurobiology of neuropsychiatric disorders. In the present study, we comprehensively examined the associations between common ADH variants [minor allele frequency (MAF) >0.05] and 11 neuropsychiatric and neurological disorders. A total of 50,063 subjects in 25 independent cohorts were analyzed. The entire ADH gene cluster was imputed across these 25 cohorts using the same reference panels. Association analyses were conducted, adjusting for multiple comparisons. We found 28 and 15 single nucleotide polymorphisms (SNPs), respectively, that were significantly associated with schizophrenia in African-Americans and autism in European-Americans after correction by false discovery rate (FDR) (q?<?0.05); and 19 and 6 SNPs, respectively, that were significantly associated with these two disorders after region-wide correction by SNPSpD (8.9?×?10??≤?em class="a-plus-plus">p??≤?.0003 and 2.4?×?10??≤?em class="a-plus-plus">p?≤?.0003, respectively). No variants were significantly associated with the other nine neuropsychiatric disorders, including alcohol dependence. We concluded that common ADH variants conferred risk for both schizophrenia in African-Americans and autism in European-Americans.