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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 Hohn
  • , Veronique Vitart
  • , Anthony P. Khawaja
  • , Kenji Yamashiro
  • , S. Mohsen Hosseini
  • , Terho Lehtimaki
  • , 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 Kahonen, Ilkka Seppala, 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 Parssinen, 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, Seang Mei Saw, Jugnoo S. Rahi, Jean François Korobelnik, John P. Kemp, Nicholas J. Timpson, George Davey Smith, Jamie E. Craig, Kathryn P. Burdon, Rhys D. Fogarty, Sudha K. Iyengar, Emily Chew, Sarayut Janmahasatian, Nicholas G. Martin, Stuart MacGregor, Liang Xu, Maria Schache, Vinay Nangia, Songhomitra Panda-Jonas, Alan F. Wright, Jeremy R. Fondran, Jonathan H. Lass, Sheng Feng, Jing Hua Zhao, Kay Tee Khaw, Nick J. Wareham, Taina Rantanen, Jaakko Kaprio, Chi Pui Pang, Li Jia Chen, Pancy O. Tam, Vishal Jhanji, Alvin L. Young, Angela Doring, Leslie J. Raffel, Mary Frances Cotch, Xiaohui Li, Shea Ping Yip, Maurice K.H. Yap, Ginevra Biino, Simona Vaccargiu, Maurizio Fossarello, Brian Fleck, Seyhan Yazar, Jan Willem L. Tideman, Milly Tedja, Margaret M. Deangelis, Margaux Morrison, Lindsay Farrer, Xiangtian Zhou, Wei Chen, Nobuhisa Mizuki, Akira Meguro, Kari Matti Makela
  • Singapore National Eye Center
  • Duke-NUS Medical School
  • Erasmus University Rotterdam
  • National Institutes of Health
  • Johns Hopkins University
  • National University of Singapore
  • King's College London
  • Cardiff University
  • Johannes Gutenberg University Mainz
  • University of Bern
  • University of Edinburgh
  • University of Cambridge
  • Kyoto University
  • University of Toronto
  • Tampere University
  • Queensland Institute of Medical Research
  • University of Tartu
  • University of Melbourne
  • Université de Bordeaux
  • Institut national de la santé et de la recherche médicale
  • National Research Council of Italy
  • University of Helsinki
  • University College London
  • University of Tasmania
  • Sun Yat-Sen University
  • University of Split
  • Sisters of Charity Hospital
  • University of Bristol
  • Max Planck Institute for Psycholinguistics
  • University of Queensland
  • University of Tennessee Health Science Center
  • Case Western Reserve University
  • Dardenne Eye Hospital
  • Université de Lille
  • University of Turku
  • University of Hamburg
  • Helmholtz Zentrum München - German Research Center for Environmental Health
  • Technical University of Munich
  • Netherlands Genomics Initiative
  • Capital Medical University
  • Tan Tock Seng Hospital
  • Agency for Science, Technology and Research, Singapore
  • Moorfields Eye Hospital NHS Foundation Trust
  • University of Wisconsin-Madison
  • The Westmead Institute for Medical Research
  • Zhongshan Ophthalmic Center
  • Jyvaskyla Central Hospital
  • University of Jyväskylä
  • Heidelberg University 
  • University of Western Australia
  • University of Pennsylvania
  • Flinders University
  • Suraj Eye Institute
  • Duke University
  • Cambridge University Hospitals NHS Foundation Trust
  • National Institute for Health and Welfare
  • Chinese University of Hong Kong
  • Prince of Wales Hospital Hong Kong
  • Cedars-Sinai Medical Center
  • University of California at Los Angeles
  • Hong Kong Polytechnic University
  • NHS Lothian
  • University of Utah
  • Boston University
  • Wenzhou Medical University
  • Yokohama City University

Research output: Contribution to journalArticlepeer-review

128 Scopus citations

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.

Original languageEnglish
Article number11008
JournalNature Communications
Volume7
DOIs
StatePublished - Mar 29 2016

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