@article{2641f8690cae419f8973075bfb4f71ed,
title = "Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium",
abstract = "Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7-15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E-08) and 2.3% (P = 6.9E-21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E-04).",
keywords = "CREAM Consortium, Myopia, refractive error, age-dependent effects, Childhood gene-environment interactions",
author = "Qiao Fan and Xiaobo Guo and Tideman, {J. Willem L.} and Williams, {Katie M.} and Seyhan Yazar and Hosseini, {S. Mohsen} and Howe, {Laura D.} and Pourcain, {Beat{\'e} St} and Evans, {David M.} and Timpson, {Nicholas J.} and George McMahon and Hysi, {Pirro G.} and Eva Krapohl and Wang, {Ya Xing} and Jonas, {Jost B.} and Baird, {Paul Nigel} and Wang, {Jie Jin} and Cheng, {Ching Yu} and Teo, {Yik Ying} and Wong, {Tien Yin} and Xiaohu Ding and Robert Wojciechowski and Young, {Terri L.} and Olavi P{\"a}rssinen and Konrad Oexle and Norbert Pfeiffer and Bailey-Wilson, {Joan E.} and Paterson, {Andrew D.} and Klaver, {Caroline C.W.} and Robert Plomin and Hammond, {Christopher J.} and Mackey, {David A.} and Mingguang He and Saw, {Seang Mei} and Cathy Williams and Guggenheim, {Jeremy A.} and {The CREAM Consortium} and Akira Meguro and Wright, {Alan F.} and Hewitt, {Alex W.} and Young, {Alvin L.} and Veluchamy, {Amutha Barathi} and Andres Metspalu and Angela D{\"o}ring and Khawaja, {Anthony P.} and Klein, {Barbara E.} and Brian Fleck and Klaver, {Caroline C.W.} and Caroline Hayward and C{\'e}cile Delcourt and Pang, {Chi Pui} and Khor, {Chiea Chuen} and Christian Gieger and Simpson, {Claire L.} and {Van Duijn}, {Cornelia M.} and Dwight Stambolian and Emily Chew and Tai, {E. Shyong} and Evelin Mihailov and Smith, {George Davey} and Ginevra Biino and Harry Campbell and Igor Rudan and Ilkka Sepp{\"a}l{\"a} and Jaakko Kaprio and Wilson, {James F.} and Craig, {Jamie E.} and Ried, {Janina S.} and Korobelnik, {Jean Fran{\c c}ois} and Fondran, {Jeremy R.} and Jiemin Liao and Zhao, {Jing Hua} and Jing Xie and Kemp, {John P.} and Lass, {Jonathan H.} and Rahi, {Jugnoo S.} and Juho Wedenoja and M{\"a}kel{\"a}, {Kari Matti} and Burdon, {Kathryn P.} and Khaw, {Kay Tee} and Kenji Yamashiro and Chen, {Li Jia} and Liang Xu and Lindsay Farrer and Ikram, {M. Kamran} and Deangelis, {Margaret M.} and Margaux Morrison and Maria Schache and Mario Pirastu and Masahiro Miyake and Yap, {Maurice K.H.} and Maurizio Fossarello and Mika K{\"a}h{\"o}nen and Tedja, {Milly S.} and Nagahisa Yoshimura and Martin, {Nicholas G.} and Wareham, {Nick J.} and Nobuhisa Mizuki and Olli Raitakari and Ozren Polasek and Tam, {Pancy O.} and Foster, {Paul J.} and Paul Mitchell and Peng Chen and Phillippa Cumberland and Puya Gharahkhani and Ren{\'e} H{\"o}hn and Fogarty, {Rhys D.} and Luben, {Robert N.} and Igo, {Robert P.} and Ronald Klein and Sarayut Janmahasatian and Yip, {Shea Ping} and Sheng Feng and Simona Vaccargiu and Songhomitra Panda-Jonas and Stuart MacGregor and Iyengar, {Sudha K.} and Taina Rantanen and Terho Lehtim{\"a}ki and Thomas Meitinger and Tin Aung and Toomas Haller and Veronique Vitart and Vinay Nangia and Verhoeven, {Virginie J.M.} and Vishal Jhanji and Wanting Zhao and Wei Chen and Xiangtian Zhou and Yi Lu and Zoran Vatavuk",
year = "2016",
month = may,
day = "13",
doi = "10.1038/srep25853",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}