Journal article
Quantile regression analysis reveals widespread evidence for gene-environment or gene-gene interactions in myopia development
A Pozarickij, C Williams, PG Hysi, JA Guggenheim, T Aslam, SA Barman, JH Barrett, P Bishop, P Blows, C Bunce, RO Carare, U Chakravarthy, M Chan, SYL Chua, DP Crabb, PM Cumberland, A Day, P Desai, B Dhillon, AD Dick Show all
Communications Biology | NATURE PUBLISHING GROUP | Published : 2019
Open access
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). LA..
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Awarded by Scottish Government
Funding Acknowledgements
This research has been conducted using the UK Biobank Resource (applications #17351). We thank Arkan Abadi and David Meyre (McMaster University) for advice on R codes. The work was funded by the National Eye Research Centre grant SAC015 (JAG, CW), and an NIHR Senior Research Fellowship award SRF-2015-08-005 (CW). UK Biobank was established by the Wellcome Trust; the UK Medical Research Council; the Department for Health (London, UK); Scottish Government (Edinburgh, UK); and the Northwest Regional Development Agency (Warrington, UK). It also received funding from the Welsh Assembly Government (Cardiff, UK); the British Heart Foundation; and Diabetes UK. Collection of eye and vision data was supported by The Department for Health through an award made by the NIHR to the Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust, and UCL Institute of Ophthalmology, London, United Kingdom (grant no. BRC2_009). Additional support was provided by The Special Trustees of Moorfields Eye Hospital, London, United Kingdom (grant no. ST 12 09). Data analysis was carried out using the RAVEN computing cluster, maintained by the ARCCA group at Cardiff University ARCCA and the BLUE CRYSTAL3 computing cluster maintained by the HPC group at the University of Bristol.