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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
Source: Scientific reports, 13 2016, v. 6, no. , p. 1-14
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).
Publisher: Nature Publishing Group
Journal: Scientific reports 
EISSN: 2045-2322
DOI: 10.1038/srep25853
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
The following publication Fan, Q. et al. 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) is available at
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