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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, JWL
Williams, KM
Yazar, S
Hosseini, SM
Howe, LD
Pourcain, BS
Evans, DM
Timpson, NJ
McMahon, G
Hysi, PG
Krapohl, E
Wang, YX
Jonas, JB
Baird, PN
Wang, JJ
Cheng, CY
Teo, YY
Wong, TY
Ding, X
Wojciechowski, R
Young, TL
Pärssinen, O
Oexle, K
Pfeiffer, N
Bailey-Wilson, JE
Paterson, AD
Klaver, CCW
Plomin, R
Hammond, CJ
He, M
Saw, SM
Guggenheim, JA
Meguro, A
Wright, AF
Hewitt, AW
Young, AL
Veluchamy, AB
Metspalu, A
Döring, A
Khawaja, AP
Klein, BE
St, Pourcain, B
Fleck, B
Klaver, CCW
Hayward, C
Williams, C
Delcourt, C
Pang, CP
Khor, CC
Gieger, C
Simpson, CL
Van, Duijn, CM
Mackey, DA
Stambolian, D
Chew, E
Tai, ES
Mihailov, E
Smith, GD
Biino, G
Campbell, H
Rudan, I
Seppälä, I
Kaprio, J
Wilson, JF
Craig, JE
Ried, JS
Korobelnik, JF
Fondran, JR
Liao, J
Zhao, JH
Xie, J
Kemp, JP
Lass, JH
Rahi, JS
Wedenoja, J
Mäkelä, KM
Burdon, KP
Khaw, KT
Yamashiro, K
Chen, LJ
Xu, L
Farrer, L
Ikram, MK
Deangelis, MM
Morrison, M
Schache, M
Pirastu, M
Miyake, M
Yap, MKH 
Fossarello, M
Kähönen, M
Tedja, MS
Yoshimura, N
Martin, NG
Wareham, NJ
Mizuki, N
Raitakari, O
Polasek, O
Tam, PO
Foster, PJ
Mitchell, P
Chen, P
Cumberland, P
Gharahkhani, P
Höhn, R
Fogarty, RD
Luben, RN
Igo, RP
Klein, R
Janmahasatian, S
Yip, SP
Feng, S
Vaccargiu, S
Panda-Jonas, S
MacGregor, S
Iyengar, SK
Rantanen, T
Lehtimäki, T
Meitinger, T
Aung, T
Haller, T
Vitart, V
Nangia, V
Verhoeven, VJM
Jhanji, V
Zhao, W
Chen, W
Zhou, X
Lu, Y
Vatavuk, Z
Issue Date: 2016
Publisher: Nature Publishing Group
Source: Scientific reports, 2016, v. 6 , 25853 How to cite?
Journal: Scientific reports 
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).
EISSN: 2045-2322
DOI: 10.1038/srep25853
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