Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium

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• 作者：Virginie J. M. Verhoeven (12)
  Pirro G. Hysi (3)
  Seang-Mei Saw (45)
  Veronique Vitart (6)
  Alireza Mirshahi (7)
  Jeremy A. Guggenheim (8)
  Mary Frances Cotch (9)
  Kenji Yamashiro (10)
  Paul N. Baird (11)
  David A. Mackey (1112)
  Robert Wojciechowski (1314)
  M. Kamran Ikram (1215)
  Alex W. Hewitt (11)
  Priya Duggal (13)
  Sarayut Janmahasatian (16)
  Chiea-Chuen Khor (17)
  Qiao Fan (4)
  Xin Zhou (4)
  Terri L. Young (18)
  E-Shyong Tai (19)
  Liang-Kee Goh (420)
  Yi-Ju Li (18)
  Tin Aung (515)
  Eranga Vithana (515)
  Yik-Ying Teo (42122)
  Wanting Tay (5)
  Xueling Sim (22)
  Igor Rudan (23)
  Caroline Hayward (6)
  Alan F. Wright (6)
  Ozren Polasek (24)
  Harry Campbell (23)
  James F. Wilson (23)
  Brian W. Fleck (25)
  Isao Nakata (10)
  Nagahisa Yoshimura (10)
  Ryo Yamada (26)
  Fumihiko Matsuda (26)
  Kyoko Ohno-Matsui (27)
  Abhishek Nag (3)
  George McMahon (28)
  Beate St. Pourcain (28)
  Yi Lu (29)
  Jugnoo S. Rahi (3031)
  Phillippa M. Cumberland (3032)
  Shomi Bhattacharya (31)
  Claire L. Simpson (14)
  Larry D. Atwood (33)
  Xiaohui Li (34)
  Leslie J. Raffel (34)
  Federico Murgia (35)
  Laura Portas (35)
  Dominiek D. G. Despriet (12)
  Leonieke M. E. van Koolwijk (236)
  Christian Wolfram (7)
  Karl J. Lackner (737)
  Anke T?njes (3839)
  Reedik M?gi (4041)
  Terho Lehtim?ki (4243)
  Mika K?h?nen (4445)
  T?nu Esko (40)
  Andres Metspalu (40)
  Taina Rantanen (46)
  Olavi P?rssinen (47)
  Barbara E. Klein (48)
  Thomas Meitinger (4950)
  Timothy D. Spector (3)
  Ben A. Oostra (51)
  Albert V. Smith (5253)
  Paulus T. V. M. de Jong (6254)
  Albert Hofman (2)
  Najaf Amin (2)
  Lennart C. Karssen (2)
  Fernando Rivadeneira (255)
  Johannes R. Vingerling (12)
  Gueny Eiríksdóttir (53)
  Vilmundur Gudnason (5253)
  Angela D?ring (63)
  Thomas Bettecken (56)
  André G. Uitterlinden (255)
  Cathy Williams (57)
  Tanja Zeller (58)
  Rapha?le Castagné (59)
  Konrad Oexle (50)
  Cornelia M. van Duijn (2)
  Sudha K. Iyengar (16)
  Paul Mitchell (60)
  Jie Jin Wang (1160)
  René H?hn (7)
  Norbert Pfeiffer (7)
  Joan E. Bailey-Wilson (14)
  Dwight Stambolian (61)
  Tien-Yin Wong (4515)
  Christopher J. Hammond (3)
  Caroline C. W. Klaver (12) c.c.w.klaver@erasmusmc.nl
• 刊名：Human Genetics
• 出版年：2012
• 出版时间：September 2012
• 年：2012
• 卷：131
• 期：9
• 页码：1467-1480
• 全文大小：493.6 KB
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• 作者单位：1. Department of Ophthalmology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands2. Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands3. Department of Twin Research and Genetic Epidemiology, King’s College London, St. Thomas-Hospital, London, UK4. Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore5. Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore6. Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK7. Department of Ophthalmology, J. Gutenberg University Medical Center, Mainz, Germany8. School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK9. Division of Epidemiology and Clinical Applications, National Eye Institute, Intramural Research Program, National Institutes of Health, Bethesda, USA10. Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan11. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia12. Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia13. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA14. Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, USA15. Department of Ophthalmology, National University Health System, National University of Singapore, Singapore, Singapore16. Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, USA17. Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore18. Center for Human Genetics, Duke University Medical Center, Durham, USA19. Department of Medicine, National University of Singapore, Singapore, Singapore20. Duke-National University of Singapore Graduate Medical School, Singapore, Singapore21. Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore22. Centre for Molecular Epidemiology, National University of Singapore, Singapore, Singapore23. Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK24. Faculty of Medicine, University of Split, Split, Croatia25. Princess Alexandra Eye Pavilion, Edinburgh, UK26. Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan27. Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, Japan28. School of Social and Community Medicine, University of Bristol, Bristol, UK29. Department of Genetics and Population Health, Queensland Institute of Medical Research, Brisbane, Australia30. Medical Research Council Centre of Epidemiology for Child Health, Institute of Child Health, University College London, London, UK31. Institute of Ophthalmology, University College London, London, UK32. Ulverscroft Vision Research Group, University College London, London, UK33. Department of Neurology, Boston University School of Medicine, Boston, USA34. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, USA35. Institute of Population Genetics, National Research Council, Sassari, Italy36. Glaucoma Service, The Rotterdam Eye Hospital, Rotterdam, The Netherlands37. Institute of Clinical Chemistry and Laboratory Medicine, J. Gutenberg University Medical Center, Mainz, Germany38. Department of Medicine, University of Leipzig, Leipzig, Germany39. Integrated Research and Treatment Center (IFB) AdiposityDiseases, University of Leipzig, Leipzig, Germany40. Estonian Genome Center, University of Tartu, Tartu, Estonia41. The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK42. Department of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital, Tampere, Finland43. University of Tampere School of Medicine, Tampere, Finland44. Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland45. Department of Clinical Physiology, University of Tampere School of Medicine, Tampere, Finland46. Department of Health Sciences, Gerontology Research Center, University of Jyv?skyl?, Jyv?skyl?, Finland47. Department of Ophthalmology, Central Hospital of Central Finland, Jyv?skyl?, Finland48. Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, USA49. Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology I, Neuherberg, Germany50. Institute of Human Genetics, Technical University Munich, Munich, Germany51. Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands52. Department of Medicine, University of Iceland, Reykjavik, Iceland53. Icelandic Heart Association, Kopavogur, Iceland54. Department of Clinical and Molecular Ophthalmogenetics, Netherlands Institute of Neurosciences (NIN), An Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands55. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands56. Center for Applied Genotyping, Max Planck Institute of Psychiatry, German Research Institute of Psychiatry, Munich, Germany57. Centre for Child and Adolescent Health, University of Bristol, Bristol, UK58. Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany59. INSERM UMRS 937, Pierre and Marie Curie University (UPMC, Paris 6) and Medical School, Paris, France60. Department of Ophthalmology, Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Sydney, Australia61. Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA62. Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands63. Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Neuherberg, Germany
• ISSN：1432-1203

文摘

Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87 × 10?12 for SNP rs634990 in Caucasians, and 9.65 × 10?4 for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 × 10?23 for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95 % CI 1.64, 2.16, P < 0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95 % CI 1.19, 1.49, P < 0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (P value 5.81 × 10?2 for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide.