| 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; 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 |
| Publisher Information: |
NATURE PORTFOLIO |
| Publication Year: |
2016 |
| Collection: |
The University of Melbourne: Digital Repository |
| 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). |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2045-2322 |
| Relation: |
pii: srep25853; https://hdl.handle.net/11343/262475 |
| Availability: |
https://hdl.handle.net/11343/262475 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; CC BY |
| Accession Number: |
edsbas.730BF0F6 |
| Database: |
BASE |