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, Tariq Aslam, Sarah A. Barman, Paul Bishop, Peter Blows, Catey Bunce, Roxana O. Carare, Usha Chakravarthy, Michelle Chan, Sharon Y. L. Chua, David P. Crabb, Philippa M. Cumberland, Alexander Day, Parul Desai, Bal Dhillon, Andrew D. DickCathy Egan, Sarah Ennis, Paul Foster, Marcus Fruttiger, John E. J. Gallacher, David F. Garway-Heath, Jane Gibson, Dan Gore, Chris J. Hammond, Alison Hardcastle, Simon P. Harding, Ruth E. Hogg, Pearse A. Keane, Sir Peng T. Khaw, Anthony P. Khawaja, Gerassimos Lascaratos, Andrew J. Lotery, Tom Mac Gillivray, Sarah Mackie, Keith Martin, Michelle McGaughey, Bernadette McGuinness, Gareth J. McKay, Martin McKibbin, Danny Mitry, Tony Moore, Zaynah A. Muthy, Eoin O'Sullivan, Chris G. Owen, Praveen Patel, Ananth C. Viswanathan

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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
JournalCommunications Biology
Issue number1
Early online date6 May 2019
Publication statusPublished - Dec 2019


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