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

Qiao Fan, Virginie Verhoeven, Robert Wojciechowski, Veluchamy Barathi, Pirro Hysi, Jeremy Guggenheim, Rene Hohn, Veronique Vitart, Anthony Khawaja, Kenji Yamashiro, S Hosseini, Terho Lehtimaki, Yi Lu, Toomas Haller, Jing Xie, Cécile Delcourt, Mario Pirastu, Juho Wedenoja, Puya Gharahkhani, Cristina VenturiniMasahiro Miyake, Alex Hewitt, Xiaobo Guo, Johanna Mazur, Jenifer Huffman, Katie Williams, Ozren Polasek, Harry Campbell, Igor Rudan, Zoran Vatavuk, James Wilson, Peter Joshi, George McMahon, Beate St. Pourcain, David Evans, Claire Simpson, Tai-Hwi Schantes-An, Robert Igo, Alireza Mirshahi, Audrey Cougnard-Gregoire, Céline Bellenguez, Maria Blettner, Olli Raitakari, Mika Kahonen, Ilkka Seppala, Tanja Zeller, Thomas Meitinger, Janina Ried, Christian Gieger, Laura Portas, Elisabeth Van Leeuwen, Najaf Amin, André Uitterlinden, Fernando Rivadeneira, Albert Hofman, Johannes Vingerling, Ya Xing Wang, Wang Xu, Eileen Boh, M Kamran Ikram, Charumathi Sabanayagam, Preeti Gupti, Vincent Tan, Zhou Lei, Candice Ho, Wan'e Lim, Roger Beuerman, Rosalynn Siantar, E-Shyong Tai, Eranga Vithana, Evelin Mihailov, Chiea-Chuen Khor, Caroline Hayward, Robert Luben, Paul Foster, Barbara Klein, Ronald Klein, Hoi Wong, Paul Mitchell, Andres Metspalu, Tin Aung, Terri Young, Mingguang He, Olavi Parssinen, Cornelia van Duijn, Jie Wang, Cathy Williams, Jost Jonas, Yik-Ying Teo, David Mackey, Konrad Oexle, Nagahisa Yoshimura, Andrew Paterson, Norbert Pfeiffer, Tien-Yin Wong, Paul Baird, Dwight Stambolian, Joan Bailey-Wilson, Ching-Yu Cheng, Christopher Hammond, Caroline Klaver, Seang-Mei Saw, Jugnoo Rahi, Jean-Francois Korobelnik, John Kemp, Nicholas Timpson, George Smith, Jamie Craig, Kathryn Burdon, Rhys Fogarty, Sudha Iyengar, Emily Chew, Sarayut Janmahasatian, Nicholas Martin, Stuart Macgregor, Liang Xu, Maria Schache, Vinay Nangia, Songhomitra Panda-Jones, Alan Wright, Jeremy Fondran, Jonathan Lass, Sheng Feng, Jing Zhao, Kay-Tee Khaw, Nicholas Wareham, Taina Rantanen, Jaako Kaprio, Chi Pui Pang, Li Chen, Pancy Tam, Vishal Jhanji, Alvin Youn, Angela Doring, Leslie Raffel, Mary Cotch, Xiaohui Liu, Shea Yip, Maurice Yap, Ginevra Biino, Simona Vaccargiu, Maurizio Fossarello, Brian Fleck, Seyhan Yazar, Jan Tideman, Milly Tedja, Margaret Deangelis, Margaux Morrison, Lindsay Ferrer, Xiangtian Zhou, Wei Chen, Nobuhisa Mizuki, Akira Meguro, Kari Makela

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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<8.5 × 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
Number of pages12
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 2016

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    Fan, Q., Verhoeven, V., Wojciechowski, R., Barathi, V., Hysi, P., Guggenheim, J., Hohn, R., Vitart, V., Khawaja, A., Yamashiro, K., Hosseini, S., Lehtimaki, T., Lu, Y., Haller, T., Xie, J., Delcourt, C., Pirastu, M., Wedenoja, J., Gharahkhani, P., ... Makela, K. (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