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

Pozarickij, Alfred, Williams, Cathy, Hysi, Pirro G., Guggenheim, Jeremy ORCID: https://orcid.org/0000-0001-5164-340X and Consortium, UK Biobank Eye and Vision 2019. Quantile regression analysis reveals widespread evidence for gene-environment or gene-gene interactions in myopia development. Communications Biology 2 , 167. 10.1038/s42003-019-0387-5

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Abstract

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
Date Type:	Publication
Status:	Published
Schools:	Optometry and Vision Sciences
Publisher:	Nature Research
ISSN:	2399-3642
Funders:	National Eye Research Centre, NIHR
Date of First Compliant Deposit:	5 April 2019
Date of Acceptance:	15 March 2019
Last Modified:	04 May 2023 23:56
URI:	https://orca.cardiff.ac.uk/id/eprint/121524

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