| Contributors: |
Fan, Q; Guo, X; Tideman, Jw; Williams, Km; Yazar, S; Hosseini, Sm; Howe, Ld; Pourcain, B; 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, Cc; Plomin, R; Hammond, Cj; Mackey, Da; He, M; Saw, Sm; Williams, C; Guggenheim, Ja; CREAM Consortium Meguro, A; Wright, Af; Hewitt, Aw; Young, Al; Veluchamy, Ab; Metspalu, A; Döring, A; Khawaja, Ap; Klein, Be; Fleck, B; Hayward, C; Delcourt, C; Pang, Cp; Khor, Cc; Gieger, C; Simpson, Cl; van Duijn, Cm; Stambolian, D; Chew, E; Tai, E; Mihailov, E; Smith, Gd; Biino, G; Campbell, H; Rudan, I; Seppälä, I; Kaprio, J; Wilson, Jf; Craig, Je; Ried, J; Korobelnik, Jf; Fondran, Jr; Liao, J; Zhao, Jh; Xie, J; Kemp, Jp; Lass, Jh; Rahi, J; Wedenoja, J; Mäkelä, Km; Burdon, Kp; Khaw, Kt; Yamashiro, K; Chen, Lj; Xu, L; Farrer, L |
| Description: |
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) |