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Fan, Q.* ; Guo, X.* ; Tideman, J.W.L.* ; Williams, K.M.* ; Yazar, S.* ; Hosseini, S.M.* ; Howe, L.D.* ; Pourcain, B.S.* ; Evans, D.M.* ; Timpson, N.J.* ; McMahon, G.* ; Hysi, P.G.* ; Krapohl, E.* ; Wang, Y.X.* ; Jonas, J.B.* ; Baird, P.N.* ; Wang, J.J.* ; Cheng, C.Y.* ; Teo, Y.Y.* ; Wong, T.Y.* ; Ding, X.* ; Wojciechowski, R.* ; Young, T.L.* ; Pärssinen, O.* ; Oexle, K.* ; Pfeiffer, N.* ; Bailey-Wilson, J.E.* ; Paterson, A.D.* ; Klaver, C.C.W.* ; Plomin, R.* ; Hammond, C.J.* ; He, M.* ; Saw, S.M.* ; Guggenheim, J.A.* ; Meguro, A.* ; Wright, A.F.* ; Hewitt, A.W.* ; Young, A.L.* ; Veluchamy, A.B.* ; Metspalu, A.* ; The CREAM Consortium (Döring, A. ; Gieger, C. ; Ried, J.S.) ; Khawaja, A.P.* ; Klein, B.E.* ; St Pourcain, B.* ; Fleck, B.* ; Hayward, C.* ; Williams, C.* ; Delcourt, C.* ; Pang, C.P.* ; Khor, C.C.* ; Simpson, C.L.* ; van Duijn, C.M.* ; Mackey, D.A.* ; Stambolian, D.* ; Chew, E.* ; Tai, E.S.* ; Mihailov, E.* ; Smith, G.D.* ; Biino, G.* ; Campbell, H.* ; Rudan, I.* ; Seppälä, I.* ; Kaprio, J.* ; Wilson, J.F.* ; Craig, J.E.*

Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium.

Sci. Rep. 6:25853 (2016)
Publ. Version/Full Text Research data DOI
Open Access Gold
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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).
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Quellenangaben Volume: 6, Issue: , Pages: , Article Number: 25853 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed