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

Fan, Qiao, Guo, Xiabo, Tideman, J. Willem L., Williams, Katie M., Yazar, Seyhan, Hosseini, Mohsen, Howe, Laura D., Pourcain, Beate St, Evans, David M., Timpson, Nicholas J., McMahon, George, Hysi, Pirro G., Krapohl, Eva, Wang, Ya Xing, Jonas, Jost B., Baird, Paul N., Wang, Jie Jin, Cheng, Ching-Yu, Teo, Yik-Yin, Wong, Tien-Yin, Ding, Xiaohu, Wojciechowski, Robert, Young, Terri L., Parssinen, Olavi, Oexle, Konrad, Pfeiffer, Norbert, Bailey-Wilson, Joan E., Patterson, Andrew D., Klaver, Caroline C. W., Plomin, Robert, Hammond, Christopher J., Mackey, David A., He, Mingguang, Saw, Seang-Mei, Williams, Cathy and Guggenheim, Jeremy Andrew 2016. Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium. Scientific Reports 6 , -. 10.1038/srep25853

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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 Type: Article
Date Type: Publication
Status: Published
Schools: Optometry and Vision Sciences
Advanced Research Computing @ Cardiff (ARCCA)
Subjects: R Medicine > RE Ophthalmology
Additional Information: Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/2045-2322/ (accessed 26/04/2016)
Publisher: Nature Publishing Group
ISSN: 2045-2322
Date of First Compliant Deposit: 25 April 2016
Date of Acceptance: 25 April 2016
Last Modified: 27 Aug 2019 11:00
URI: http://orca.cf.ac.uk/id/eprint/89909

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