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Christopher J. Hammond, Pirro G. Hysi, Samantha J. Fahy, Tim D. Spector; Genome-wide Association Study Of Nuclear And Cortical Cataract Identifies Potential Genes And Pathways That Alter Susceptibility To The Disease. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5911.
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© ARVO (1962-2015); The Authors (2016-present)
Our twin study has previously suggested around 50% of variation in nuclear and cortical cataract is explained by genetic factors. While we and others have reported the EPHA2 gene as associated with cortical cataract, little is known about inherited risk factors that determine individual susceptibility to age-related cataract.
Quantitative phenotypes related to lens opacity were obtained on 2895 subjects from the TwinsUK cohort over the age of 50 years (mean 63, SD 7.0), all were of European ancestry and 90% female. Nuclear cataract was assessed using digital Scheimpflug lens photography, and cortical cataract scored by grading of retroillumination images (Marcher Instruments, Hereford, UK). Genome-wide Association Studies were performed using the Illumina HumanHap 300k Duo and the HumanHap610-Quad arrays. Imputation was calculated with reference to HapMap release 22 CEU population data using IMPUTE version 2. Analysis was performed using Merlin. Association findings were compared with similar GWAs results from other populations of similar ancestry (including the AREDS cohort).
Genome-Wide Associations identified suggestive loci whose polymorphisms appear to alter susceptibility to cataract, both cortical (chr10q22.1 and q26) and nuclear (chr13q21.31). Of particular interest is the enriched presence of interesting functional pathways such as those involved in cell growth regulation, apoptosis or pathways that overlap with those leading to systemic lupus erythematosus. While some functional properties are in line with previously existing knowledge of the etiology of cataract, identification of novel pathways hints at a broader spectrum of factors that can cause cataract.
This work has suggested interesting new candidate loci that may alter the susceptibility to cataract. They also highlight the importance of integrating different sources of information such as genetic, functional annotation and previous literature reviewing in generating novel information about human disease.
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