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Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Fan, Qiao 
Guo, Xiaobo 
Tideman, J Willem L 
Williams, Katie M 
Yazar, Seyhan 

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).

Description

Keywords

Adolescent, Age of Onset, Asian People, Child, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Longitudinal Studies, Male, Myopia, Polymorphism, Single Nucleotide, Refractive Errors, White People

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

6

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MC_UU_12015/1)
MRC (MC_PC_13048)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
Medical Research Council (G1000143)
Medical Research Council (G0401527)
Medical Research Council (MR/N003284/1)
Medical Research Council (MC_U106179471)
TCC (None)
Medical Research Council (G0401527/1)