Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep25853
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
Caucasian
child
female
genetic predisposition
genetics
genome-wide association study
genotype environment interaction
human
longitudinal study
male
myopia
onset age
refraction error
single nucleotide polymorphism
Adolescent
Age of Onset
Asian Continental Ancestry Group
Child
European Continental Ancestry Group
Female
Gene-Environment Interaction
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Longitudinal Studies
Male
Myopia
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. https://doi.org/10.1038/srep25853
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
URI: https://scholarbank.nus.edu.sg/handle/10635/174967
ISSN: 20452322
DOI: 10.1038/srep25853
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