机构：[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 ofHealth, 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 ofTwin Research and Genetic Epidemiology, King’s College London School of Medicine, London SE1 7EH, UK[9]School of Optometry and Vision Sciences, CardiffUniversity, Cardiff CF24 4HQ, UK[10]Department of Ophthalmology, University Medical Center Mainz, 55131 Mainz, Germany[11]Department ofOphthalmology, Inselspital, University Hospital Bern, CH-3010 Bern, Switzerland[12]Medical Research Council Human Genetics Unit, Institute of Genetics andMolecular 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 UniversityGraduate School of Medicine, Kyoto 6068507, Japan[15]Program in Genetics and Genome Biology, The Hospital for Sick Children and Institute for MedicalSciences, 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), RoyalVictorian Eye and Ear Hospital, University of Melbourne, Melbourne, Victoria 3002, Australia[20]Universite´ de Bordeaux, ISPED (Institut de Sante´ Publiqued’E´pide´miologie et de De´veloppement), 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 StatisticalScience, 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, LondonSE1 7EH, UK[30]Faculty of Medicine, University of Split, Split 21000, Croatia[31]Usher Institute for Population Health Sciences and Informatics, University ofEdinburgh, 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 QueenslandDiamantina 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 ReserveUniversity, 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]Universite´ 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 ClinicalPhysiology, Tampere University Hospital and School of Medicine, University of Tampere, Tampere 33520, Finland[46]Clinic for General and InterventionalCardiology, University Heart Center Hamburg, 20246 Hamburg, Germany[47]Institute of Human Genetics, Helmholtz Zentrum Mu¨nchen, 85764Neuherberg, Germany[48]Institute of Human Genetics, Klinikum rechts der Isar, Technische Universita¨t Mu¨nchen, 81675 Munich, Germany[49]Institute ofGenetic Epidemiology, Helmholtz Zentrum Mu¨nchen—German Research Center for Environmental Health, 85764 Neuherberg, Germany[50]Department ofInternal Medicine, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands[51]Netherlands Consortium for Healthy Ageing, Netherlands GenomicsInitiative, 2518 AD Hague, The Netherlands[52]Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing 100044,China研究所眼科研究所首都医科大学附属北京同仁医院首都医科大学附属同仁医院[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 ofSingapore, Singapore 119228, Singapore[56]Division of Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore[57]Division of Geneticsand Epidemiology, UCL Institute of Ophthalmology, London EC1V 9EL, UK[58]NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS FoundationTrust and UCL Institute of Ophthalmology, London EC1V 2PD, UK[59]Department of Ophthalmology and Visual Sciences, University of Wisconsin School ofMedicine and Public Health, Madison, Wisconsin 53726, USA[60]Department of Ophthalmology, Centre for Vision Research, Westmead Institute for MedicalResearch, University of Sydney, Sydney, New South Wales 2145, Australia[61]Department of Ophthalmology and Visual Sciences, School of Medicine andPublic Health, University of Wisconsin, Madison, Wisconsin 53705, USA[62]State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun YatSen University, Guangzhou 510060, China[63]Department of Ophthalmology, Central Hospital of Central Finland, Jyva¨skyla¨ 40620, Finland[64]GerontologyResearch Center and Department of Health Sciences, University of Jyva¨skyla¨, Jyva¨skyla¨ 40014, Finland[65]Medical Faculty Mannheim, Department ofOphthalmology, Ruprecht-Karls-University Heidelberg, 69115 Mannheim, Germany[66]Department of Statistics and Applied Probability, National University ofSingapore, Singapore 117546, Singapore[67]Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, WesternAustralia 6009, Australia[68]Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA[69]Medical Research Council Centre of Epidemiology for Child Health, Institute of Child Health, University College London, London WC1E 6BT, UK[70]Instituteof Ophthalmology, Moorfields Eye Hospital, London EC1V 2PD, UK[71]Ulverscroft Vision Research Group, University College London, London WC1E 6BT, UK[72]Universite´ de Bordeaux, 33400 Talence, France[73]INSERM (Institut National de la Sante´ Et de la Recherche Me´dicale), ISPED (Institut de Sante´ Publiqued’E´pide´miologie et de De´veloppement), Centre INSERM U897-Epidemiologie-Biostatistique, 33076 Bordeaux, France[74]MRC Integrative Epidemiology Unit(IEU), The University of Bristol, Bristol BS8 2BN, UK[75]Department of Ophthalmology, Flinders University, Adelaide, South Australia 5001, Australia[76]Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio 44106, USA[77]Department of Ophthalmology and VisualSciences, Case Western Reserve University and University Hospitals Eye Institute, Cleveland, Ohio 44106, USA[78]Department of Genetics, Case WesternReserve University, Cleveland, Ohio 44106, USA[79]National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA[80]GeneticEpidemiology Laboratory, QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland 4029, Australia[81]Suraj Eye Institute, Nagpur,Maharashtra 440001, India[82]Department of Pediatric Ophthalmology, Duke Eye Center For Human Genetics, Durham, North Carolina 27710, USA[83]MRC Epidemiology Unit, Institute of Metabolic Sciences, University of Cambridge, Cambridge CB2 1TN, UK[84]MRC Epidemiology Unit, Institute ofMetabolic Science, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK[85]Gerontology Research Center, University of Jyva¨skyla¨, Jyva¨skyla¨ 40014, Finland[86]Department of Public Health, University of Helsinki, Helsinki 00014, Finland[87]Institute for Molecular Medicine, University of Helsinki, Helsinki 00014,Finland[88]Department of Mental Health and Alcohol Abuse Services, National Institute for Health and Welfare, Helsinki 00271, Finland[89]Department ofOphthalmology and Visual Sciences, Hong Kong Eye Hospital, The Chinese University of Hong Kong, Kowloon, Hong Kong[90]Department of Ophthalmologyand Visual Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong[91]Institute of Epidemiology I, Helmholtz ZentrumMu¨nchen, German Research Center for Environmental Health, 85764 Neuherberg, Germany[92]Institute of Epidemiology II, Helmholtz Zentrum Mu¨nchen,German Research Center for Environmental Health, 85764 Neuherberg, Germany[93]Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles,California 90048, USA[94]Division of Epidemiology and Clinical Applications, National Eye Institute, Bethesda, Maryland 20892, USA[95]Institute forTranslational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Los Angeles, California 90502,USA[96]Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, Hong Kong[97]Institute of Molecular Genetics,National Research Council, Pavia 27100, Italy[98]Princess Alexandra Eye Pavilion, Edinburgh EH3 9HA, UK[99]Department of Ophthalmology and VisualSciences, Moran Eye Center, University of Utah, Salt Lake City, Utah 84132, USA[100]Department of Ophthalmology and Visual Sciences, John Moran EyeCenter, University of Utah, Salt Lake City, Utah 84132, USA[101]Departments of Medicine (Biomedical Genetics), Ophthalmology, Neurology, Epidemiologyand Biostatistics, Boston University Schools of Medicine and Public Health, Boston, Massachusetts 02118, USA[102]School of ophthalmology and optometry,Wenzhou Medical University, Wenzhou 325035, China[103]Department of Ophthalmology, Yokohama City University School of Medicine,Yokohama, Kanagawa 236-0027, Japan[104]Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere,Tampere 33014, Finland.
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 x 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 x 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.
基金：
MRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [MR/N003284/1, MC_UU_12013/4, MR/K023721/1, MC_UU_12013/1, MC_UU_12015/1, MC_PC_U127561128, MC_UU_12013/3] Funding Source: UKRI; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [MC_PC_13048, 1201677] Funding Source: researchfish; National Institute for Health ResearchNational Institute for Health Research (NIHR) [NF-SI-0512-10114, SRF-2015-08-005, SRF/01/010] Funding Source: researchfish; NATIONAL EYE INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Eye Institute (NEI) [K08EY022943, ZIAEY000403, ZIAEY000401, R01EY024233, R01EY014685] Funding Source: NIH RePORTER; NATIONAL HUMAN GENOME RESEARCH INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [ZIAHG200327] Funding Source: NIH RePORTER; Department of HealthEuropean Commission [SRF/01/010] Funding Source: Medline; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [MC_UU_12013/1, MC_UU_12013/3, G0401527, MC_PC_15018, MC_U106179471, MR/N003284/1, MC_UU_12015/1, MR/K023721/1, MR/K006584/1, MC_UU_12013/4, MC_PC_U127561128, G9815508] Funding Source: Medline; NEI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Eye Institute (NEI) [R01 EY024233, K08 EY022943, R01 EY014685] Funding Source: Medline; Wellcome TrustWellcome TrustEuropean Commission [102215] Funding Source: Medline
第一作者机构：[1]Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 169856, Singapore[2]Duke-NUS Medical School, Singapore 169857, Singapore
共同第一作者：
通讯作者：
通讯机构：[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[7]Department of Ophthalmology, National University Health Systems, National University of Singapore Singapore 119228, Singapore[53]Saw Swee Hock School of Public Health, National University of Singapore and National University Health Systems, Singapore 117549, Singapore
推荐引用方式(GB/T 7714)：
Qiao Fan,Virginie J.M. Verhoeven,Robert Wojciechowski,et al.Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error[J].NATURE COMMUNICATIONS.2016,7:doi:10.1038/ncomms11008.
APA：
Qiao Fan,Virginie J.M. Verhoeven,Robert Wojciechowski,Veluchamy A. Barathi,Pirro G.Hysi...&Consortium for Refractive Error and Myopia (CREAM).(2016).Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error.NATURE COMMUNICATIONS,7,
MLA：
Qiao Fan,et al."Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error".NATURE COMMUNICATIONS 7.(2016)
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