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Journal Article

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

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St Pourcain,  Beate
University of Bristol, Bristol, Avon, England ;
Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society;
Duke NUS Medial Sch, Ctr Quantitat Med, Singapore, Singapore;
Population genetics of human communication, MPI for Psycholinguistics, Max Planck Society;

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srep25853.pdf
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Supplementary Material (public)

srep25853-s1.pdf
(Supplementary material), 2MB

Citation

Fan, Q., Guo, X., Tideman, J. W. L., Williams, K. M., Yazar, S., Hosseini, S. M., et al. (2016). Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium. Scientific Reports, 6: 25853. doi:10.1038/srep25853.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002A-C605-A
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).