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Matthew P Johnson, Suman S Thapa, Kent L Anderson, Bradford Towne, Janardan Subedi, John Blangero, Sarah Williams-Blangero; Genetic epidemiology of ocular health and disease in eastern Nepal: The Jiri Eye Study (JES). Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1249.
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Approximately 90% (n=660 million) of the world’s visually impaired reside in developing countries. Combating ocular-related health problems in these countries is critical if we are to reduce the global burden associated with visual impairment (VI). The primary objective of a new study established in eastern Nepal and focused on the Jirel ethnic group is to identify rare functional variants that influence VI. Nepal is a developing country where the prevalence of VI across regions ranges from 7% to 42%.
Our family-based study design will recruit 2,000 members of the Jirel population to undergo, likely for the first time, an eye examination to document, in part, the prevalence of ocular diseases known to influence VI (e.g., age-related cataract, glaucoma). We will use SOLAR to determine the underlying genetic architecture (heritability, pleiotropy) of all measured ocular-related traits and disease end-points. An existing high-density framework of genetic variants will be used in a joint linkage/association analysis procedure to localize genomic regions (QTLs) most likely to harbor ocular candidate genes. An exome sequencing strategy will be employed to objectively prioritize rare functional variants influencing ocular QTLs. An independent, population-based cohort (n=2,200) from the Bhaktapur District of Nepal will be used to replicate findings.
The Jirels belong to a single extended pedigree containing >62,000 pair-wise relationships that are informative for genetic analysis. The Jirel pedigree has 80% power to detect an additive genetic heritability as low as 6.5%, a genetic correlation between two traits as low as 4.4%, and a genetic association explaining as little as 1.1% of the variation observed in a tested trait. The 316 founders of the Jirel pedigree could maximally transmit 10 to 112 copies of a private variant. The average probability that one of the Jirel founders disseminates five extra copies of a private variant ranges from 0.20 to 0.92.
The Jirel population is ideal for identifying functional rare variants due to its genetic isolation and deep genealogical relationships. Results from our well-powered study design will explicitly implicate genes in causal biological pathways influencing VI trait variance and therefore, encourage testing of these genes in other global populations.
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