Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium.
Scientific reports 2016 ; 6: 25853.
Fan Q, Guo X, Tideman JW, 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 CC, Plomin R, Hammond CJ, Mackey DA, He M, Saw SM, Williams C, Guggenheim JA, and CREAM Consortium
DOI : 10.1038/srep25853
PubMed ID : 27174397
PMCID : PMC4865831
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).