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Title: Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium
Authors: 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
Döring, A
Khawaja, A.P
Klein, B.E
St Pourcain, B
Fleck, B
Klaver, C.C.W
Hayward, C
Williams, C
Delcourt, C
Pang, C.P
Khor, C.-C 
Gieger, 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
Ried, J.S
Korobelnik, J.-F
Fondran, J.R
Liao, J 
Zhao, J.H
Xie, J
Kemp, J.P
Lass, J.H
Rahi, J.S
Wedenoja, J
Mäkelä, K.-M
Burdon, K.P
Khaw, K.-T
Yamashiro, K
Chen, L.J
Xu, L
Farrer, L
Ikram, M.K 
Deangelis, M.M
Morrison, M
Schache, M
Pirastu, M
Miyake, M
Yap, M.K.H
Fossarello, M
Kähönen, M
Tedja, M.S
Yoshimura, N
Martin, N.G
Wareham, N.J
Mizuki, N
Raitakari, O
Polasek, O
Tam, P.O
Foster, P.J
Mitchell, P
Chen, P 
Cumberland, P
Gharahkhani, P
Höhn, R
Fogarty, R.D
Luben, R.N
Igo, R.P
Klein, R
Janmahasatian, S
Yip, S.P
Feng, S
Vaccargiu, S
Panda-Jonas, S
MacGregor, S
Iyengar, S.K
Rantanen, T
Lehtimäki, T
Meitinger, T
Aung, T 
Haller, T
Vitart, V
Nangia, V
Verhoeven, V.J.M
Jhanji, V
Zhao, W
Chen, W
Zhou, X
Lu, Y
Vatavuk, Z
The CREAM Consortium
Keywords: adolescent
Asian continental ancestry group
genetic predisposition
genome-wide association study
genotype environment interaction
longitudinal study
onset age
refraction error
single nucleotide polymorphism
Age of Onset
Asian Continental Ancestry Group
European Continental Ancestry Group
Gene-Environment Interaction
Genetic Predisposition to Disease
Genome-Wide Association Study
Longitudinal Studies
Polymorphism, Single Nucleotide
Refractive Errors
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: 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, Döring, A, Khawaja, A.P, Klein, B.E, St Pourcain, B, Fleck, B, Klaver, C.C.W, Hayward, C, Williams, C, Delcourt, C, Pang, C.P, Khor, C.-C, Gieger, 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, Ried, J.S, Korobelnik, J.-F, Fondran, J.R, Liao, J, Zhao, J.H, Xie, J, Kemp, J.P, Lass, J.H, Rahi, J.S, Wedenoja, J, Mäkelä, K.-M, Burdon, K.P, Khaw, K.-T, Yamashiro, K, Chen, L.J, Xu, L, Farrer, L, Ikram, M.K, Deangelis, M.M, Morrison, M, Schache, M, Pirastu, M, Miyake, M, Yap, M.K.H, Fossarello, M, Kähönen, M, Tedja, M.S, Yoshimura, N, Martin, N.G, Wareham, N.J, Mizuki, N, Raitakari, O, Polasek, O, Tam, P.O, Foster, P.J, Mitchell, P, Chen, P, Cumberland, P, Gharahkhani, P, Höhn, R, Fogarty, R.D, Luben, R.N, Igo, R.P, Klein, R, Janmahasatian, S, Yip, S.P, Feng, S, Vaccargiu, S, Panda-Jonas, S, MacGregor, S, Iyengar, S.K, Rantanen, T, Lehtimäki, T, Meitinger, T, Aung, T, Haller, T, Vitart, V, Nangia, V, Verhoeven, V.J.M, Jhanji, V, Zhao, W, Chen, W, Zhou, X, Lu, Y, Vatavuk, Z, The CREAM Consortium (2016). Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium. Scientific Reports 6 : 25853. ScholarBank@NUS Repository.
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).
Source Title: Scientific Reports
ISSN: 20452322
DOI: 10.1038/srep25853
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