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Jugnoo S. Rahi, Pirro G. Hysi, Christopher J. Hammond, Andrew R. Webster, Shomi S. Bhattacharya, Pak C. Sham; Functional Pathways Participating In Myopia: Identification Through Genome-wide Association Studies. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2519.
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Myopia and hyperopia - deviations from the spherical equivalent mean - are the most common ophthalmic conditions. They can affect quality of life and those with high myopia are at risk of blindness. Better understanding of the emmetropization processes would allow improved treatment of these conditions in the future. We undertook a Genome-Wide Association Study (GWAS) in a large population cohort to demonstrate how genetics is helping uncover physiological processes underlying myopia and hyperopia.
We conducted a full Genome Wide Association in 1,667 fully refracted participants of the British 1958 Birth Cohort, 1000 of whom had GWAS using the Illumina 1M array, and 600 with data from other arrays including the Affymetrix 1M and 500k chips, with imputation performed using Mach. The mean spherical equivalent in the panel was -0.95D (SD=2.0). Results obtained from the GWA were compared against the genome annotation and the transcripts where strongest associations were obtained were searched for enrichment of physiological pathways in functional annotation libraries. Findings were replicated in an independent cohort of 4,504 British subjects of Caucasian ancestry from the TwinsUK cohort.
The GWA replicated previously published findings of GWA for refractive error, such as the loci on chromosome 15q25 and 15q14. Several important new loci were also identified at GWA or suggestive statistical significance. Additionally these analyses found statistically significant enrichment in both populations for key pathways, such as those controlling the central nervous development and behavior, suggesting that these pathways, among others, may play important roles in the development of refraction error in the general population. Pathway-specific association analyses confirmed the primary roles played by these pathways into the etiology of refractive error.
This work highlights the intertwining between early-life and life course factors in the development of myopia or hyperopia, and in particular that genetic pathways associated with behaviour may contribute to refractive error. It also shows that identification of even small-effect genetic loci can greatly improve knowledge of human disease.
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