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

Pozarickij, A., Williams, C., Hysi, P. G., Guggenheim, J. A., Aslam, T., Barman, S. A., Barrett, J. H., Bishop, P., Blows, P., Bunce, C., Carare, R. O., Chakravarthy, U., Chan, M., Chua, S. Y. L., Crabb, D. P. ORCID: 0000-0001-8754-3902, Cumberland, P. M., Day, A., Desai, P., Dhillon, B., Dick, A. D., Egan, C., Ennis, S., Foster, P., Fruttiger, M., Gallacher, J. E. J., Garway-Heath, D. F., Gibson, J., Gore, D., Hammond, C. J., Hardcastle, A., Harding, S. P., Hogg, R. E., Keane, P. A., Khaw, S. P. T., Khawaja, A. P., Lascaratos, G., Lotery, A. J., Mac Gillivray, T., Mackie, S., Martin, K., McGaughey, M., McGuinness, B., McKay, G. J., McKibbin, M., Mitry, D., Moore, T., Morgan, J. E., Muthy, Z. A., O’Sullivan, E., Owen, C. G., Patel, P., Paterson, E., Peto, T., Petzold, A., Rahi, J. S., Rudnikca, A. R., Self, J., Sivaprasad, S., Steel, D., Stratton, I., Strouthidis, N., Sudlow, C., Thomas, D., Trucco, E., Tufail, A., Vitart, V., Vernon, S. A., Viswanathan, A. C., Williams, K., Woodside, J. V., Yates, M. M., Yip, J. and Zheng, Y. (2019). Quantile regression analysis reveals widespread evidence for gene-environment or gene-gene interactions in myopia development. Communications Biology, 2(1), 167.. doi: 10.1038/s42003-019-0387-5

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.

Publication Type: Article
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RE Ophthalmology
Departments: School of Health Sciences > Optometry & Visual Science
URI: http://openaccess.city.ac.uk/id/eprint/22744
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