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

Author

Listed:
  • Qiao Fan

    (Singapore Eye Research Institute, Singapore National Eye Centre
    Duke-NUS Medical School)

  • Virginie J. M. Verhoeven

    (Erasmus Medical Center
    Erasmus Medical Center)

  • Robert Wojciechowski

    (Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health
    Johns Hopkins Bloomberg School of Public Health)

  • Veluchamy A. Barathi

    (Singapore Eye Research Institute, Singapore National Eye Centre
    Duke-NUS Medical School
    National University Health Systems, National University of Singapore)

  • Pirro G. Hysi

    (King’s College London School of Medicine)

  • Jeremy A. Guggenheim

    (School of Optometry and Vision Sciences, Cardiff University)

  • René Höhn

    (University Medical Center Mainz
    Inselspital, University Hospital Bern)

  • Veronique Vitart

    (Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh)

  • Anthony P. Khawaja

    (Institute of Public Health, University of Cambridge School of Clinical Medicine)

  • Kenji Yamashiro

    (Kyoto University Graduate School of Medicine)

  • S Mohsen Hosseini

    (Program in Genetics and Genome Biology, The Hospital for Sick Children and Institute for Medical Sciences, University of Toronto)

  • Terho Lehtimäki

    (Fimlab Laboratories and School of Medicine, University of Tampere)

  • Yi Lu

    (Statistical Genetics Laboratory, QIMR Berghofer Medical Research Institute, Herston)

  • Toomas Haller

    (Estonian Genome Center, University of Tartu)

  • Jing Xie

    (Centre for Eye Research Australia (CERA), Royal Victorian Eye and Ear Hospital, University of Melbourne)

  • Cécile Delcourt

    (Université de Bordeaux, ISPED (Institut de Santé Publique d'Épidémiologie et de Développement)
    INSERM, U1219-Bordeaux Population Health Research Center)

  • Mario Pirastu

    (Institute of Population Genetics, National Research Council)

  • Juho Wedenoja

    (University of Helsinki
    University of Helsinki and Helsinki University Hospital)

  • Puya Gharahkhani

    (Statistical Genetics Laboratory, QIMR Berghofer Medical Research Institute, Herston)

  • Cristina Venturini

    (King’s College London School of Medicine
    UCL Institute of Ophthalmology)

  • Masahiro Miyake

    (Kyoto University Graduate School of Medicine)

  • Alex W. Hewitt

    (Centre for Eye Research Australia (CERA), Royal Victorian Eye and Ear Hospital, University of Melbourne
    Menzies Research Institute Tasmania, University of Tasmania)

  • Xiaobo Guo

    (School of Mathematics and Computational Science, Sun Yat-Sen University)

  • Johanna Mazur

    (Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz)

  • Jenifer E. Huffman

    (Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh)

  • Katie M. Williams

    (King’s College London School of Medicine
    King’s College London)

  • Ozren Polasek

    (Faculty of Medicine, University of Split)

  • Harry Campbell

    (Usher Institute for Population Health Sciences and Informatics, University of Edinburgh)

  • Igor Rudan

    (Usher Institute for Population Health Sciences and Informatics, University of Edinburgh)

  • Zoran Vatavuk

    (Sisters of Mercy University Hospital)

  • James F. Wilson

    (Usher Institute for Population Health Sciences and Informatics, University of Edinburgh)

  • Peter K. Joshi

    (Usher Institute for Population Health Sciences and Informatics, University of Edinburgh)

  • George McMahon

    (MRC Integrative Epidemiology Unit (IEU), University of Bristol
    School of Social and Community Medicine, University of Bristol)

  • Beate St Pourcain

    (MRC Integrative Epidemiology Unit (IEU), University of Bristol
    School of Social and Community Medicine, University of Bristol
    Max Planck Institute for Psycholinguistics)

  • David M. Evans

    (MRC Integrative Epidemiology Unit (IEU), University of Bristol
    School of Social and Community Medicine, University of Bristol
    University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland 4102, Australia)

  • Claire L. Simpson

    (Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health
    Genomics and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA)

  • Tae-Hwi Schwantes-An

    (Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health)

  • Robert P. Igo

    (Case Western Reserve University)

  • Alireza Mirshahi

    (University Medical Center Mainz
    Dardenne Eye Hospital, Bonn-Bad Godesberg)

  • Audrey Cougnard-Gregoire

    (Université de Bordeaux, ISPED (Institut de Santé Publique d'Épidémiologie et de Développement)
    INSERM, U1219-Bordeaux Population Health Research Center)

  • Céline Bellenguez

    (Inserm, U1167
    Univ. Lille, U1167
    Université Lille 2)

  • Maria Blettner

    (Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz)

  • Olli Raitakari

    (Research Centre of Applied and Preventive Medicine, University of Turku
    Turku University Hospital)

  • Mika Kähönen

    (Tampere University Hospital and School of Medicine, University of Tampere)

  • Ilkka Seppälä

    (Fimlab Laboratories and School of Medicine, University of Tampere)

  • Tanja Zeller

    (Clinic for General and Interventional Cardiology, University Heart Center Hamburg)

  • Thomas Meitinger

    (Institute of Human Genetics, Helmholtz Zentrum München
    Institute of Human Genetics, Klinikum rechts der Isar, Technische Universität München)

  • Janina S. Ried

    (Institute of Genetic Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health)

  • Christian Gieger

    (Institute of Genetic Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health)

  • Laura Portas

    (Institute of Population Genetics, National Research Council)

  • Elisabeth M. van Leeuwen

    (Erasmus Medical Center)

  • Najaf Amin

    (Erasmus Medical Center)

  • André G. Uitterlinden

    (Erasmus Medical Center
    Erasmus Medical Center
    Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative)

  • Fernando Rivadeneira

    (Erasmus Medical Center
    Erasmus Medical Center
    Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative)

  • Albert Hofman

    (Erasmus Medical Center
    Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative)

  • Johannes R. Vingerling

    (Erasmus Medical Center)

  • Ya Xing Wang

    (Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University)

  • Xu Wang

    (Saw Swee Hock School of Public Health, National University of Singapore and National University Health Systems)

  • Eileen Tai-Hui Boh

    (Saw Swee Hock School of Public Health, National University of Singapore and National University Health Systems)

  • M. Kamran Ikram

    (Singapore Eye Research Institute, Singapore National Eye Centre
    Duke-NUS Medical School)

  • Charumathi Sabanayagam

    (Singapore Eye Research Institute, Singapore National Eye Centre
    Duke-NUS Medical School)

  • Preeti Gupta

    (Singapore Eye Research Institute, Singapore National Eye Centre)

  • Vincent Tan

    (Singapore Eye Research Institute, Singapore National Eye Centre)

  • Lei Zhou

    (Singapore Eye Research Institute, Singapore National Eye Centre)

  • Candice E. H. Ho

    (Singapore Eye Research Institute, Singapore National Eye Centre)

  • Wan’e Lim

    (National University Health Systems, National University of Singapore)

  • Roger W. Beuerman

    (Singapore Eye Research Institute, Singapore National Eye Centre
    Duke-NUS Medical School
    National University Health Systems, National University of Singapore)

  • Rosalynn Siantar

    (Singapore Eye Research Institute, Singapore National Eye Centre
    National Healthcare Group Eye Institute, Tan Tock Seng Hospital)

  • E-Shyong Tai

    (Duke-NUS Medical School
    Saw Swee Hock School of Public Health, National University of Singapore and National University Health Systems
    National University of Singapore)

  • Eranga Vithana

    (Singapore Eye Research Institute, Singapore National Eye Centre
    Duke-NUS Medical School
    National University Health Systems, National University of Singapore)

  • Evelin Mihailov

    (Estonian Genome Center, University of Tartu)

  • Chiea-Chuen Khor

    (Singapore Eye Research Institute, Singapore National Eye Centre
    Saw Swee Hock School of Public Health, National University of Singapore and National University Health Systems
    Genome Institute of Singapore)

  • Caroline Hayward

    (Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh)

  • Robert N. Luben

    (Institute of Public Health, University of Cambridge School of Clinical Medicine)

  • Paul J. Foster

    (UCL Institute of Ophthalmology
    NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology)

  • Barbara E. K. Klein

    (University of Wisconsin School of Medicine and Public Health)

  • Ronald Klein

    (University of Wisconsin School of Medicine and Public Health)

  • Hoi-Suen Wong

    (Program in Genetics and Genome Biology, The Hospital for Sick Children and Institute for Medical Sciences, University of Toronto)

  • Paul Mitchell

    (Centre for Vision Research, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales 2145, Australia)

  • Andres Metspalu

    (Estonian Genome Center, University of Tartu)

  • Tin Aung

    (Singapore Eye Research Institute, Singapore National Eye Centre
    National University Health Systems, National University of Singapore)

  • Terri L. Young

    (School of Medicine and Public Health, University of Wisconsin)

  • Mingguang He

    (State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University)

  • Olavi Pärssinen

    (Central Hospital of Central Finland
    University of Jyväskylä)

  • Cornelia M. van Duijn

    (Erasmus Medical Center)

  • Jie Jin Wang

    (Centre for Vision Research, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales 2145, Australia)

  • Cathy Williams

    (School of Social and Community Medicine, University of Bristol)

  • Jost B. Jonas

    (Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University
    Medical Faculty Mannheim, Ruprecht-Karls-University Heidelberg)

  • Yik-Ying Teo

    (Saw Swee Hock School of Public Health, National University of Singapore and National University Health Systems
    Genome Institute of Singapore
    National University of Singapore)

  • David A. Mackey

    (Menzies Research Institute Tasmania, University of Tasmania
    Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia 6009, Australia)

  • Konrad Oexle

    (Institute of Human Genetics, Klinikum rechts der Isar, Technische Universität München)

  • Nagahisa Yoshimura

    (Kyoto University Graduate School of Medicine)

  • Andrew D. Paterson

    (Program in Genetics and Genome Biology, The Hospital for Sick Children and Institute for Medical Sciences, University of Toronto)

  • Norbert Pfeiffer

    (University Medical Center Mainz)

  • Tien-Yin Wong

    (Singapore Eye Research Institute, Singapore National Eye Centre
    Duke-NUS Medical School
    National University Health Systems, National University of Singapore
    Saw Swee Hock School of Public Health, National University of Singapore and National University Health Systems)

  • Paul N. Baird

    (Centre for Eye Research Australia (CERA), Royal Victorian Eye and Ear Hospital, University of Melbourne)

  • Dwight Stambolian

    (University of Pennsylvania)

  • Joan E. Bailey Wilson

    (Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health)

  • Ching-Yu Cheng

    (Singapore Eye Research Institute, Singapore National Eye Centre
    Duke-NUS Medical School
    National University Health Systems, National University of Singapore)

  • Christopher J. Hammond

    (King’s College London School of Medicine
    King’s College London)

  • Caroline C. W. Klaver

    (Erasmus Medical Center
    Erasmus Medical Center)

  • Seang-Mei Saw

    (Singapore Eye Research Institute, Singapore National Eye Centre
    Duke-NUS Medical School
    National University Health Systems, National University of Singapore
    Saw Swee Hock School of Public Health, National University of Singapore and National University Health Systems)

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

Suggested Citation

  • Qiao Fan & Virginie J. M. Verhoeven & Robert Wojciechowski & Veluchamy A. Barathi & Pirro G. Hysi & Jeremy A. Guggenheim & René Höhn & Veronique Vitart & Anthony P. Khawaja & Kenji Yamashiro & S Mohse, 2016. "Meta-analysis of gene–environment-wide association scans accounting for education level identifies additional loci for refractive error," Nature Communications, Nature, vol. 7(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11008
    DOI: 10.1038/ncomms11008
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