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

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

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.

Pozarickij, Alfred
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Williams, Cathy
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UK Biobank Eye and Vision Consortium
Pozarickij, Alfred
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Williams, Cathy
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Hysi, Pirro G.
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UK Biobank Eye and Vision Consortium (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).

Record type: Article

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.

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Published date: 6 May 2019

Identifiers

Local EPrints ID: 433706
URI: http://eprints.soton.ac.uk/id/eprint/433706
PURE UUID: b9ea1f7b-a93b-4fc8-a2fb-fc184f806edb
ORCID for Roxana O. Carare: ORCID iD orcid.org/0000-0001-6458-3776
ORCID for Sarah Ennis: ORCID iD orcid.org/0000-0003-2648-0869
ORCID for Jane Gibson: ORCID iD orcid.org/0000-0002-0973-8285
ORCID for Andrew J. Lotery: ORCID iD orcid.org/0000-0001-5541-4305
ORCID for Jay Self: ORCID iD orcid.org/0000-0002-1030-9963

Catalogue record

Date deposited: 02 Sep 2019 16:30
Last modified: 26 Nov 2021 02:50

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Contributors

Author: Alfred Pozarickij
Author: Cathy Williams
Author: Pirro G. Hysi
Author: Jeremy A. Guggenheim
Author: Tariq Aslam
Author: Sarah A. Barman
Author: Jenny H. Barrett
Author: Paul Bishop
Author: Peter Blows
Author: Catey Bunce
Author: Usha Chakravarthy
Author: Michelle Chan
Author: Sharon Y.L. Chua
Author: David P. Crabb
Author: Philippa M. Cumberland
Author: Alexander Day
Author: Parul Desai
Author: Bal Dhillon
Author: Andrew D. Dick
Author: Cathy Egan
Author: Sarah Ennis ORCID iD
Author: Paul Foster
Author: Marcus Fruttiger
Author: John E.J. Gallacher
Author: David F. Garway-Heath
Author: Jane Gibson ORCID iD
Author: Dan Gore
Author: Chris J. Hammond
Author: Alison Hardcastle
Author: Simon P. Harding
Author: Ruth E. Hogg
Author: Pearse A. Keane
Author: Sir Peng T. Khaw
Author: Anthony P. Khawaja
Author: Gerassimos Lascaratos
Author: Tom Mac Gillivray
Author: Sarah Mackie
Author: Keith Martin
Author: Michelle McGaughey
Author: Bernadette McGuinness
Author: Gareth J. McKay
Author: Martin McKibbin
Author: Danny Mitry
Author: Tony Moore
Author: James E. Morgan
Author: Zaynah A. Muthy
Author: Eoin O’Sullivan
Author: Jay Self ORCID iD
Corporate Author: UK Biobank Eye and Vision Consortium

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