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

Citation

Fan, Q and Guo, X and Tideman, JW and Williams, KM and Yazar, S and Hosseini, SM and Howe, LD and Pourcain, BS and Evans, DM and Timpson, NJ and McMahon, G and Hysi, PG and Krapohl, E and Wang, YX and Jonas, JB and Baird, PN and Wang, JJ and Cheng, CY and Teo, YY and Wong, TY and Ding, X and Wojciechowski, R and Young, TL and Parssinen, O and Oexle, K and Pfeiffer, N and Bailey-Wilson, JE and Paterson, AD and Klaver, CC and Plomin, R and Hammond, CJ and Mackey, DA and He, M and Saw, SM and Williams, C and Guggenheim, JA and Hewitt, AW, and the CREAM Consortium, Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium, Scientific Reports, 6 Article 25853. ISSN 2045-2322 (2016) [Refereed Article]


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Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1038/srep25853

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).

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Ophthalmology and Optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Hearing, Vision, Speech and Their Disorders
Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:122760
Year Published:2016
Web of Science® Times Cited:15
Deposited By:Menzies Institute for Medical Research
Deposited On:2017-11-27
Last Modified:2017-12-06
Downloads:18 View Download Statistics

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