Quantile regression analysis reveals widespread evidence for gene-environment or gene-gene interactions in myopia development



Pozarickij, A, Williams, C, Hysi, PG, Guggenheim, JA, Aslam, T, Barman, SA, Barrett, JH, Bishop, P, Blows, P, Bunce, C
et al (show 63 more authors) (2019) Quantile regression analysis reveals widespread evidence for gene-environment or gene-gene interactions in myopia development. Communications Biology, 2 (1).

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Abstract

© 2019, The Author(s). A genetic contribution to refractive error has been confirmed by the discovery of more than 150 associated variants in genome-wide association studies (GWAS). Environmental factors such as education and time outdoors also demonstrate strong associations. Currently however, the extent of gene-environment or gene-gene interactions in myopia is unknown. We tested the hypothesis that refractive error-associated variants exhibit effect size heterogeneity, a hallmark feature of genetic interactions. Of 146 variants tested, evidence of non-uniform, non-linear effects were observed for 66 (45%) at Bonferroni-corrected significance (P < 1.1 × 10−4) and 128 (88%) at nominal significance (P < 0.05). LAMA2 variant rs12193446, for example, had an effect size varying from −0.20 diopters (95% CI −0.18 to −0.23) to −0.89 diopters (95% CI −0.71 to −1.07) in different individuals. SNP effects were strongest at the phenotype extremes and weaker in emmetropes. A parsimonious explanation for these findings is that gene-environment or gene-gene interactions in myopia are pervasive.

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 28 Oct 2019 10:49
Last Modified: 05 Jun 2020 14:10
DOI: 10.1038/s42003-019-0387-5
URI: http://livrepository.liverpool.ac.uk/id/eprint/3059430