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

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 Mohsen Hosseini, Terho Lehtimäki, Yi Lu, Toomas Haller, Jing Xie, Cécile Delcourt, Mario Pirastu, Juho Wedenoja, Puya Gharahkhani, Cristina Venturini, Masahiro Miyake, Alex W. Hewitt, Xiaobo Guo, Johanna Mazur, Jenifer E. Huffman, Katie M. Williams, Ozren Polasek, Harry Campbell, Igor Rudan, Zoran Vatavuk, James F. Wilson, Peter K. Joshi, George McMahon, Beate St Pourcain, David M. Evans, Claire L. Simpson, Tae-Hwi Schwantes-An, Robert P. Igo, Alireza Mirshahi, Audrey Cougnard-Gregoire, Céline Bellenguez, Maria Blettner, Olli Raitakari, Mika Kähönen, Ilkka Seppälä, Tanja Zeller, Thomas Meitinger, Janina S. Ried, Christian Gieger, Laura Portas, Elisabeth M. van Leeuwen, Najaf Amin, André G. Uitterlinden, Fernando Rivadeneira, Albert Hofman, Johannes R. Vingerling, Ya Xing Wang, Xu Wang, Eileen Tai-Hui Boh, M. Kamran Ikram, Charumathi Sabanayagam, Preeti Gupta, Vincent Tan, Lei Zhou, Candice E. H. Ho, Wan’e Lim, Roger W. Beuerman, Rosalynn Siantar, E-Shyong Tai, Eranga Vithana, Evelin Mihailov, Chiea-Chuen Khor, Caroline Hayward, Robert N. Luben, Paul J. Foster, Barbara E. K. Klein, Ronald Klein, Hoi-Suen Wong, Paul Mitchell, Andres Metspalu, Tin Aung, Terri L. Young, Mingguang He, Olavi Pärssinen, Cornelia M. van Duijn, Jie Jin Wang, Cathy Williams, Jost B. Jonas, Yik-Ying Teo, David A. Mackey, Konrad Oexle, Nagahisa Yoshimura, Andrew D. Paterson, Norbert Pfeiffer, Tien-Yin Wong, Paul N. Baird, Dwight Stambolian, Joan E. Bailey Wilson, Ching-Yu Cheng, Christopher J. Hammond, Caroline C. W. Klaver () and Seang-Mei Saw ()
Additional contact information
Qiao Fan: Singapore Eye Research Institute, Singapore National Eye Centre
Virginie J. M. Verhoeven: Erasmus Medical Center
Robert Wojciechowski: Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health
Veluchamy A. Barathi: Singapore Eye Research Institute, Singapore National Eye Centre
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
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)
Mario Pirastu: Institute of Population Genetics, National Research Council
Juho Wedenoja: University of Helsinki
Puya Gharahkhani: Statistical Genetics Laboratory, QIMR Berghofer Medical Research Institute, Herston
Cristina Venturini: King’s College London School of Medicine
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
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
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
Beate St Pourcain: MRC Integrative Epidemiology Unit (IEU), University of Bristol
David M. Evans: MRC Integrative Epidemiology Unit (IEU), University of Bristol
Claire L. Simpson: Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health
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
Audrey Cougnard-Gregoire: Université de Bordeaux, ISPED (Institut de Santé Publique d'Épidémiologie et de Développement)
Céline Bellenguez: Inserm, U1167
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
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
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
Fernando Rivadeneira: Erasmus Medical Center
Albert Hofman: Erasmus Medical Center
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
Charumathi Sabanayagam: Singapore Eye Research Institute, Singapore National Eye Centre
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
Rosalynn Siantar: Singapore Eye Research Institute, Singapore National Eye Centre
E-Shyong Tai: Duke-NUS Medical School
Eranga Vithana: Singapore Eye Research Institute, Singapore National Eye Centre
Evelin Mihailov: Estonian Genome Center, University of Tartu
Chiea-Chuen Khor: Singapore Eye Research Institute, Singapore National Eye Centre
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
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
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
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
Yik-Ying Teo: Saw Swee Hock School of Public Health, National University of Singapore and National University Health Systems
David A. Mackey: Menzies Research Institute Tasmania, University of Tasmania
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
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
Christopher J. Hammond: King’s College London School of Medicine
Caroline C. W. Klaver: Erasmus Medical Center
Seang-Mei Saw: Singapore Eye Research Institute, Singapore National Eye Centre

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: 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

Date: 2016
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DOI: 10.1038/ncomms11008

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