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Exploiting genetics to understand paediatric eye disorders

Plotnikov, Denis 2020. Exploiting genetics to understand paediatric eye disorders. PhD Thesis, Cardiff University.
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The primary aim of this series of investigations was to identify causal risk factors for paediatric eye disorders (e.g. myopia, hyperopia, strabismus and amblyopia). A series of hypotheses was tested in this project by exploiting state-of-the-art genetic and epidemiological approaches such as genome-wide association studies (GWAS) and Mendelian randomisation (MR). A GWAS for strabismus was performed in order to identify genetic variant(s) conferring susceptibility to the condition. The genetic variant most strongly associated with the phenotype was rs75078292. This SNP, is situated in an LD block on chromosome 17, containing the genes TSPAN10, NPLOC4 and PDE6G. A non-synonymous variant in TSPAN10 – in very high LD with rs75078292 – was previously reported to be associated with myopia. These findings were replicated in a cohort of children (ALSPAC). A Mendelian randomisation approach (both one- and two-sample MR) was used in order to estimate the effect of birth weight within the normal range (2.5 to 4.5kg) on refractive error. The analyses supported the hypothesis that birth weight within normal range plays a causal role in refractive error development. The influence of education on refractive error development was estimated using a Regression Discontinuity design. In this work in UK Biobank, the Raising Of School Leaving Age (ROSLA) 1972 reform was used as a natural experiment; with use of the genetic data such as Principal Components and Polygenic Risk Scores for educational attainment and for refractive error as covariates. The estimated influence of an additional year of education on refractive error development was statistically significant, supporting existing evidence. The hypothesis that hyperopia is causal risk factor for lower educational attainment was tested using non-linear Mendelian randomisation analysis. The results of the analyses revealed that the relationship between refractive error and educational attainment in UK Biobank is non-linear, but did not support the main hypothesis.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Optometry and Vision Sciences
Subjects: R Medicine > RE Ophthalmology
Uncontrolled Keywords: Myopia, Genetics, Strabismus, Hyperopia, Refractive error, GWAS, Mendelian randomization
Date of First Compliant Deposit: 15 December 2020
Last Modified: 15 Dec 2020 14:32

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