Meta-analysis of gene–environment-wide association scans accounting for education level identifies additional loci for refractive error
Authors: Fan Qiao , Verhoeven Virginie J. M. , Wojciechowski Robert , Barathi Veluchamy A. , Hysi Pirro G. , Guggenheim Jeremy A. , Höhn René , Vitart Veronique , Khawaja Anthony P. , Yamashiro Kenji , Hosseini S Mohsen , Lehtimäki Terho , Lu Yi , Haller Toomas , Xie Jing , Delcourt Cécile , Pirastu Mario , Wedenoja Juho , Gharahkhani Puya , Venturini Cristina , Miyake Masahiro , Hewitt Alex W. , Guo Xiaobo , Mazur Johanna , Huffman Jenifer E. , Williams Katie M. , Polasek Ozren , Campbell Harry , Rudan Igor , Vatavuk Zoran , Wilson James F. , Joshi Peter K. , McMahon George , St Pourcain Beate , Evans David M. , Simpson Claire L. , Schwantes-An Tae-Hwi , Igo Robert P. , Mirshahi Alireza , Cougnard-Gregoire Audrey , Bellenguez Céline , Blettner Maria , Raitakari Olli , Kähönen Mika , Seppälä Ilkka , Zeller Tanja , Meitinger Thomas , Ried Janina S. , Gieger Christian , Portas Laura , van Leeuwen Elisabeth M. , Amin Najaf , Uitterlinden André G. , Rivadeneira Fernando , Hofman Albert , Vingerling Johannes R. , Wang Ya Xing , Wang Xu , Tai-Hui Boh Eileen , Ikram M. Kamran , Sabanayagam Charumathi , Gupta Preeti , Tan Vincent , Zhou Lei , Ho Candice E. H. , Lim Wan’e , Beuerman Roger W. , Siantar Rosalynn , Tai E-Shyong , Vithana Eranga , Mihailov Evelin , Khor Chiea-Chuen , Hayward Caroline , Luben Robert N. , Foster Paul J. , Klein Barbara E. K. , Klein Ronald , Wong Hoi-Suen , Mitchell Paul , Metspalu Andres , Aung Tin , Young Terri L. , He Mingguang , Pärssinen Olavi , van Duijn Cornelia M. , Jin Wang Jie , Williams Cathy , Jonas Jost B. , Teo Yik-Ying , Mackey David A. , Oexle Konrad , Yoshimura Nagahisa , Paterson Andrew D. , Pfeiffer Norbert , Wong Tien-Yin , Baird Paul N. , Stambolian Dwight , Wilson Joan E. Bailey , Cheng Ching-Yu , Hammond Christopher J. , Klaver Caroline C. W. , Saw Seang-Mei ,   Consortium for Refractive Error and Myopia (CREAM), Rahi Jugnoo S. , Korobelnik Jean-François , Kemp John P. , Timpson Nicholas J. , Smith George Davey , Craig Jamie E. , Burdon Kathryn P. , Fogarty Rhys D. , Iyengar Sudha K. , Chew Emily , Janmahasatian Sarayut , Martin Nicholas G. , MacGregor Stuart , Xu Liang , Schache Maria , Nangia Vinay , Panda-Jonas Songhomitra , Wright Alan F. , Fondran Jeremy R. , Lass Jonathan H. , Feng Sheng , Zhao Jing Hua , Khaw Kay-Tee , Wareham Nick J. , Rantanen Taina , Kaprio Jaakko , Pang Chi Pui , Chen Li Jia , Tam Pancy O. , Jhanji Vishal , Young Alvin L. , Döring Angela , Raffel Leslie J. , Cotch Mary-Frances , Li Xiaohui , Yip Shea Ping , Yap Maurice K.H. , Biino Ginevra , Vaccargiu Simona , Fossarello Maurizio , Fleck Brian , Yazar Seyhan , Tideman Jan Willem L. , Tedja Milly , Deangelis Margaret M. , Morrison Margaux , Farrer Lindsay , Zhou Xiangtian , Chen Wei , Mizuki Nobuhisa , Meguro Akira , Mäkelä Kari Matti 
Published: March 2016

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.