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

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

Research output: Contribution to journalArticleAcademicpeer-review

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
JournalCommunications Biology
Volume2
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

Cite this

Pozarickij, A., Williams, C., Hysi, P. G., Guggenheim, J. A., & 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]. https://doi.org/10.1038/s42003-019-0387-5
Pozarickij, Alfred ; Williams, Cathy ; Hysi, Pirro G. ; Guggenheim, Jeremy A. ; UK Biobank Eye and Vision Consortium. / Quantile regression analysis reveals widespread evidence for gene-environment or gene-gene interactions in myopia development. In: Communications Biology. 2019 ; Vol. 2, No. 1.
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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.",
author = "Alfred Pozarickij and Cathy Williams and Hysi, {Pirro G.} and Guggenheim, {Jeremy A.} and Tariq Aslam and Barman, {Sarah A.} and Barrett, {Jenny H.} and Paul Bishop and Peter Blows and Catey Bunce and Carare, {Roxana O.} and Usha Chakravarthy and Michelle Chan and Chua, {Sharon Y. L.} and Crabb, {David P.} and Cumberland, {Philippa M.} and Alexander Day and Parul Desai and Bal Dhillon and Dick, {Andrew D.} and Cathy Egan and Sarah Ennis and Paul Foster and Marcus Fruttiger and Gallacher, {John E. J.} and Garway-Heath, {David F.} and Jane Gibson and Dan Gore and Hammond, {Chris J.} and Alison Hardcastle and Harding, {Simon P.} and Hogg, {Ruth E.} and Keane, {Pearse A.} and Khaw, {Sir Peng T.} and Khawaja, {Anthony P.} and Gerassimos Lascaratos and Lotery, {Andrew J.} and {Mac Gillivray}, Tom and Sarah Mackie and Keith Martin and Michelle McGaughey and Bernadette McGuinness and McKay, {Gareth J.} and Martin McKibbin and Danny Mitry and Tony Moore and Morgan, {James E.} and Muthy, {Zaynah A.} and Axel Petzold and Y. Zheng and J. Yip and Yates, {Max M.} and {UK Biobank Eye and Vision Consortium}",
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Quantile regression analysis reveals widespread evidence for gene-environment or gene-gene interactions in myopia development. / Pozarickij, Alfred; Williams, Cathy; Hysi, Pirro G.; Guggenheim, Jeremy A.; UK Biobank Eye and Vision Consortium.

In: Communications Biology, Vol. 2, No. 1, 167, 01.12.2019.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Hardcastle, Alison

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AU - Hogg, Ruth E.

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AU - Khaw, Sir Peng T.

AU - Khawaja, Anthony P.

AU - Lascaratos, Gerassimos

AU - Lotery, Andrew J.

AU - Mac Gillivray, Tom

AU - Mackie, Sarah

AU - Martin, Keith

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AU - McGuinness, Bernadette

AU - McKay, Gareth J.

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AU - Moore, Tony

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AU - Zheng, Y.

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N2 - 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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