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 VenturiniMasahiro 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

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

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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<8.5x10-5), 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
Number of pages12
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 6 Apr 2016

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  • Projects

    MRC UoB UNITE Unit - programme 3

    Timpson, N. J. & Timpson, N. J.

    1/06/1331/03/18

    Project: Research

    MRC UoB UNITE Unit - Programme 1

    Davey Smith, G.

    1/06/1331/03/18

    Project: Research

    Cite this

    Fan, Q., Verhoeven, V. J. M., Wojciechowski, R., Barathi, V. A., Hysi, P. G., Guggenheim, J. A., Hohn, R., Vitart, V., Khawaja, A. P., Yamashiro, K., Hosseini, S. M., Lehtimaki, T., Lu, Y., Haller, T., Xie, J., Delcourt, C., Pirastu, M., Wedenoja, J., Gharahkhani, P., ... Makela, K. M. (2016). Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error. Nature Communications, 7, [11008]. https://doi.org/10.1038/ncomms11008