Gene-environment interactions in myopia

Myopia, as a common ocular disorder, is caused by both genetic and environmental factors. Conventional genome-wide association studies (GWAS) in humans have limited power to detect myopia genes partly due to the complex interplay between genes and environment. Here, I performed a GWAS in a sample of...

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Main Author: Huang, Yu
Published: Cardiff University 2018
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Online Access:https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.753593
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spelling ndltd-bl.uk-oai-ethos.bl.uk-7535932019-02-05T03:34:33ZGene-environment interactions in myopiaHuang, Yu2018Myopia, as a common ocular disorder, is caused by both genetic and environmental factors. Conventional genome-wide association studies (GWAS) in humans have limited power to detect myopia genes partly due to the complex interplay between genes and environment. Here, I performed a GWAS in a sample of chicks with form deprivation (FD) myopia, aiming to reduce environmental complexity and increase the statistical power to detect genetic variants that confer susceptibility to this environmentally-induced myopia phenotype. The degree of FD myopia was quantified by measuring the treatment-induced changes in axial length (∆AXL) and mean spherical equivalent (∆MSE). Body weight, sex, and batch were evaluated as potential confounding factors. To reduce costs, chicks in the phenotype extremes (lowest or highest ∆AXL, within each batch) were selected for genotyping. To identify genetic variants conferring susceptibility to myopia, GWA analyses for ∆AXL and ∆MSE were applied to the genotype data. After adjusting for confounding factors, genetic variant rs317386235, located between the genes PRKAR2B and PIK3CG exceeded the Bonferroni corrected significance threshold for ∆AXL. To complement the GWAS findings, an RNA sequencing transcriptomics analysis was performed, using retinal tissue from the treated and control eyes of chicks with high or low-susceptibility to myopia. This revealed 516 differentially-expressed genes, identified using a combination of three analysis tools. In order to discover more about the biological function underlying the GWAS and transcriptomics analysis results, pathway analyses were conducted. The pathway analysis implicated gene sets relating to circadian rhythms, extracellular matrix (ECM) and structural remodelling, energy generation, oxidative stress, glycometabolism and lipid metabolism.RE OphthalmologyCardiff Universityhttps://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.753593http://orca.cf.ac.uk/114604/Electronic Thesis or Dissertation
collection NDLTD
sources NDLTD
topic RE Ophthalmology
spellingShingle RE Ophthalmology
Huang, Yu
Gene-environment interactions in myopia
description Myopia, as a common ocular disorder, is caused by both genetic and environmental factors. Conventional genome-wide association studies (GWAS) in humans have limited power to detect myopia genes partly due to the complex interplay between genes and environment. Here, I performed a GWAS in a sample of chicks with form deprivation (FD) myopia, aiming to reduce environmental complexity and increase the statistical power to detect genetic variants that confer susceptibility to this environmentally-induced myopia phenotype. The degree of FD myopia was quantified by measuring the treatment-induced changes in axial length (∆AXL) and mean spherical equivalent (∆MSE). Body weight, sex, and batch were evaluated as potential confounding factors. To reduce costs, chicks in the phenotype extremes (lowest or highest ∆AXL, within each batch) were selected for genotyping. To identify genetic variants conferring susceptibility to myopia, GWA analyses for ∆AXL and ∆MSE were applied to the genotype data. After adjusting for confounding factors, genetic variant rs317386235, located between the genes PRKAR2B and PIK3CG exceeded the Bonferroni corrected significance threshold for ∆AXL. To complement the GWAS findings, an RNA sequencing transcriptomics analysis was performed, using retinal tissue from the treated and control eyes of chicks with high or low-susceptibility to myopia. This revealed 516 differentially-expressed genes, identified using a combination of three analysis tools. In order to discover more about the biological function underlying the GWAS and transcriptomics analysis results, pathway analyses were conducted. The pathway analysis implicated gene sets relating to circadian rhythms, extracellular matrix (ECM) and structural remodelling, energy generation, oxidative stress, glycometabolism and lipid metabolism.
author Huang, Yu
author_facet Huang, Yu
author_sort Huang, Yu
title Gene-environment interactions in myopia
title_short Gene-environment interactions in myopia
title_full Gene-environment interactions in myopia
title_fullStr Gene-environment interactions in myopia
title_full_unstemmed Gene-environment interactions in myopia
title_sort gene-environment interactions in myopia
publisher Cardiff University
publishDate 2018
url https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.753593
work_keys_str_mv AT huangyu geneenvironmentinteractionsinmyopia
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