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

UK Biobank Eye and Vision Consortium, Alfred Pozarickij, Cathy Williams, Pirro G. Hysi, Jeremy A. Guggenheim

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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.

Original languageEnglish
Article number167
Pages (from-to)1-8
Number of pages8
JournalCommunications Biology
Volume2
Early online date6 May 2019
DOIs
Publication statusPublished - 2019

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UK Biobank Eye and Vision Consortium, Pozarickij, A., Williams, C., Hysi, P. G., & Guggenheim, J. A. (2019). Quantile regression analysis reveals widespread evidence for gene-environment or gene-gene interactions in myopia development. Communications Biology, 2, 1-8. [167]. https://doi.org/10.1038/s42003-019-0387-5