Gene-environment and gene-gene interactions in myopia

Pozarickij, Alfred 2019. Gene-environment and gene-gene interactions in myopia. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Motivated by the release of the UK Biobank data and the lack of documented gene-environment (GxE) and gene-gene (GxG) interactions in myopia, I sought to apply various statistical tools to provide a quantitative assessment of the interplay between environmental and genetic risk factors shaping refractive error. The comparison between the two different risk measurement scales with which GxE interactions can be identified suggested that the additive risk scale can lead to a more informative perspective about refractive error aetiology. The evaluation of two indirect methods for detecting genetic variants affecting refractive error via interaction effects suggested the enrichment of GxG and GxE among the variants that display marginal SNP effects. For genetic variants already known from prior GWAS studies to influence refractive error, genetic effect sizes were highly non-uniform; individuals from the tails of the refractive error distribution (i.e. high myopes and hyperopes) displayed much larger effects compared to individuals in the middle of the distribution (i.e. emmetropes). Prediction of refractive error using GxE interactions indicated that although some of the variance of refractive error could be explained by a risk score constructed using interaction effects, the contribution of GxE was already accounted for by a risk score constructed using marginal SNP effects only. Although a handful of candidate genes were identified using multifactor dimensionality reduction technique, none displayed compelling evidence of involvement in a GxG interaction. There was, however, suggestive evidence that the candidate genes constitute a genetic interaction network which is regulated by hub gene ZMAT4. In summary, the analyses reported in this thesis provide further support for the challenging nature of definitively identifying loci involved in GxE and GxG interactions. The thesis provides several guidelines that future studies could take into account to obtain more insightful results regarding the extent of interactions in refractive error.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Optometry and Vision Sciences
Subjects:	R Medicine > RE Ophthalmology
Uncontrolled Keywords:	Myopia, refractive error, genetics
Date of First Compliant Deposit:	30 April 2020
Last Modified:	29 Apr 2021 15:55
URI:	https://orca.cardiff.ac.uk/id/eprint/131277

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