Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium
Tideman JW; Yazar S; McMahon G; Teo YY; Wang YX; Hammond CJ; Baird PN; Wang JJ; Hosseini SM; Saw SM; Plomin R; Guggenheim JA; The CREAM Consortium; Howe LD; He M; Pourcain BS; Klaver CC; Guo X; Wong TY; Pfeiffer N; Wojciechowski R; Paterson AD; Cheng CY; Fan Q; Oexle K; Williams C; Williams KM; Timpson NJ; Mackey DA; Krapohl E; Bailey-Wilson JE; Ding X; Pärssinen O; Hysi PG; Jonas JB; Evans DM; Young TL
https://urn.fi/URN:NBN:fi-fe2021042716193
Tiivistelmä
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).
Kokoelmat
- Rinnakkaistallenteet [19207]