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Nat Commun. 2016 Mar 29;7:11008. doi: 10.1038/ncomms11008.

Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error.

Fan Q1,2, Verhoeven VJ3,4, Wojciechowski R5,6, Barathi VA1,2,7, Hysi PG8, Guggenheim JA9, Höhn R10,11, Vitart V12, Khawaja AP13, Yamashiro K14, Hosseini SM15, Lehtimäki T16, Lu Y17, Haller T18, Xie J19, Delcourt C20,21, Pirastu M22, Wedenoja J23,24, Gharahkhani P17, Venturini C8,25, Miyake M14, Hewitt AW19,26, Guo X27, Mazur J28, Huffman JE12, Williams KM8,29, Polasek O30, Campbell H31, Rudan I31, Vatavuk Z32, Wilson JF31, Joshi PK31, McMahon G33,34, St Pourcain B33,34,35, Evans DM33,34,36, Simpson CL5,37, Schwantes-An TH5, Igo RP38, Mirshahi A10,39, Cougnard-Gregoire A20,21, Bellenguez C40,41,42, Blettner M28, Raitakari O43,44, Kähönen M45, Seppala I16, Zeller T46, Meitinger T47,48; Consortium for Refractive Error and Myopia, Ried JS49, Gieger C49, Portas L22, van Leeuwen EM4, Amin N4, Uitterlinden AG4,50,51, Rivadeneira F4,50,51, Hofman A4,51, Vingerling JR3, Wang YX52, Wang X53, Tai-Hui Boh E53, Ikram MK1,2, Sabanayagam C1,2, Gupta P1, Tan V1, Zhou L1, Ho CE1, Lim W7, Beuerman RW1,2,7, Siantar R1,54, Tai ES2,53,55, Vithana E1,2,7, Mihailov E18, Khor CC1,53,56, Hayward C12, Luben RN13, Foster PJ57,58, Klein BE59, Klein R59, Wong HS15, Mitchell P60, Metspalu A18, Aung T1,7, Young TL61, He M62, Pärssinen O63,64, van Duijn CM4, Jin Wang J60, Williams C34, Jonas JB52,65, Teo YY53,56,66, Mackey DA26,67, Oexle K48, Yoshimura N14, Paterson AD15, Pfeiffer N10, Wong TY1,2,7,53, Baird PN19, Stambolian D68, Wilson JE5, Cheng CY1,2,7, Hammond CJ8,29, Klaver CC3,4, Saw SM1,2,7,53, Rahi JS, Korobelnik JF, Kemp JP, Timpson NJ, Smith GD, Craig JE, Burdon KP, Fogarty RD, Iyengar SK, Chew E, Janmahasatian S, Martin NG, MacGregor S17, Xu L52, Schache M19, Nangia V, Panda-Jonas S, Wright AF12, Fondran JR, Lass JH, Feng S, Zhao JH, Khaw KT13, Wareham NJ, Rantanen T, Kaprio J, Pang CP, Chen LJ, Tam PO, Jhanji V, Young AL, Döring A, Raffel LJ, Cotch MF, Li X, Yip SP, Yap MK, Biino G, Vaccargiu S22, Fossarello M22, Fleck B, Yazar S19,67, Tideman JW3,4, Tedja M3,4, Deangelis MM, Morrison M, Farrer L, Zhou X, Chen W, Mizuki N, Meguro A, Mäkelä KM.

Author information

1
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 169856, Singapore.
2
Duke-NUS Medical School, Singapore 169857, Singapore.
3
Department of Ophthalmology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
4
Department of Epidemiology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
5
Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland 21224, USA.
6
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 20205, USA.
7
Department of Ophthalmology, National University Health Systems, National University of Singapore Singapore 119228, Singapore.
8
Department of Twin Research and Genetic Epidemiology, King's College London School of Medicine, London SE1 7EH, UK.
9
School of Optometry and Vision Sciences, Cardiff University, Cardiff CF24 4HQ, UK.
10
Department of Ophthalmology, University Medical Center Mainz, 55131 Mainz, Germany.
11
Department of Ophthalmology, Inselspital, University Hospital Bern, CH-3010 Bern, Switzerland.
12
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, Scotland.
13
Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge CB2 0SR, UK.
14
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan.
15
Program in Genetics and Genome Biology, The Hospital for Sick Children and Institute for Medical Sciences, University of Toronto, Toronto Ontario, Canada M5G 1X8.
16
Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere 33520, Finland.
17
Statistical Genetics Laboratory, QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4029, Australia.
18
Estonian Genome Center, University of Tartu, Tartu 51010, Estonia.
19
Centre for Eye Research Australia (CERA), Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Victoria 3002, Australia.
20
Université de Bordeaux, ISPED (Institut de Santé Publique d'Épidémiologie et de Développement), Bordeaux 33000, France.
21
INSERM, U1219-Bordeaux Population Health Research Center, Bordeaux 33000, France.
22
Institute of Population Genetics, National Research Council, Sassari 07100, Italy.
23
Department of Public Health, University of Helsinki, Helsinki 00014, Finland.
24
Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki 00014, Finland.
25
UCL Institute of Ophthalmology, London SE1 7EH, UK.
26
Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania 7000, Australia.
27
Department of Statistical Science, School of Mathematics and Computational Science, Sun Yat-Sen University, Guangzhou 510275, China.
28
Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz, 55131 Mainz, Germany.
29
Department of Ophthalmology, King's College London, London SE1 7EH, UK.
30
Faculty of Medicine, University of Split, Split 21000, Croatia.
31
Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, Scotland.
32
Department of Ophthalmology, Sisters of Mercy University Hospital, Zagreb 10000, Croatia.
33
MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol BS8 2BN, UK.
34
School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK.
35
Max Planck Institute for Psycholinguistics, Wundtlaan 1, 6525 XD Nijmegen, The Netherlands.
36
University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland 4102, Australia.
37
Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
38
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio 44106, USA.
39
Dardenne Eye Hospital, Bonn-Bad Godesberg, 53177 Bonn, Germany.
40
Inserm, U1167, Lille 59000, France.
41
Univ. Lille, U1167, Lille 59000, France.
42
Université Lille 2, Lille 59000, France.
43
Research Centre of Applied and Preventive Medicine, University of Turku, Turku 20520, Finland.
44
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku 20520, Finland.
45
Department of Clinical Physiology, Tampere University Hospital and School of Medicine, University of Tampere, Tampere 33520, Finland.
46
Clinic for General and Interventional Cardiology, University Heart Center Hamburg, 20246 Hamburg, Germany.
47
Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
48
Institute of Human Genetics, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
49
Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, 85764 Neuherberg, Germany.
50
Department of Internal Medicine, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
51
Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, 2518 AD Hague, The Netherlands.
52
Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing 100044, China.
53
Saw Swee Hock School of Public Health, National University of Singapore and National University Health Systems, Singapore 117549, Singapore.
54
National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore 308433, Singapore.
55
Department of Medicine, National University of Singapore, Singapore 119228, Singapore.
56
Division of Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore.
57
Division of Genetics and Epidemiology, UCL Institute of Ophthalmology, London EC1V 9EL, UK.
58
NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London EC1V 2PD, UK.
59
Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53726, USA.
60
Department of Ophthalmology, Centre for Vision Research, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales 2145, Australia.
61
Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin 53705, USA.
62
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China.
63
Department of Ophthalmology, Central Hospital of Central Finland, Jyväskylä 40620, Finland.
64
Gerontology Research Center and Department of Health Sciences, University of Jyväskylä, Jyväskylä 40014, Finland.
65
Medical Faculty Mannheim, Department of Ophthalmology, Ruprecht-Karls-University Heidelberg, 69115 Mannheim, Germany.
66
Department of Statistics and Applied Probability, National University of Singapore, Singapore 117546, Singapore.
67
Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia 6009, Australia.
68
Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Abstract

Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.

PMID:
27020472
PMCID:
PMC4820539
DOI:
10.1038/ncomms11008
[Indexed for MEDLINE]
Free PMC Article

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