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Tin Aung, Mineo Ozaki, Francesca Pasutto, Rand R Allingham, Unnur Thorsteinsdottir, Jamie E Craig, Fotis Topouzis, Yuri Astakhov, Periasamy Sundaresan, Chiea-Chuen Khor; World-wide genome-wide association study for exfoliation syndrome identifies 4 novel genetic loci.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):No Pagination Specified. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Exfoliation syndrome (XFS) is an age-related systemic disease that is associated with increased risk for glaucoma. We recently reported a genome-wide association study (GWAS) identifying CACNA1A as associated with XFS (Nature Genetics 2015; 47:387-92). To further dissect the genetic architecture underling XFS susceptibility, we now expand the GWAS to include a large number of cases and controls from 6 continents around the world.
We performed an expanded genome-wide association analysis (GWAS) on 9,700 XFS cases and 98,000 controls from 24 countries in 6 continents. Meta-analysis summarizing the results across all cohorts was performed using fixed effects modeling weighted in an inverse-variance manner.
We confirm strong association at LOXL1 (multiple SNPs) and CACNA1A rs4926244 in this new, expanded GWAS discovery collection. We also note genome-wide significant association (P<1x10-8) at four novel genetic loci. These signals map to Chromosome 6p (P = 8.5 x 10-9), 6q (P = 1.1 x 10-9), 11q (P = 1.86 x 10-9), and 13p (P = 6 x 10-10). We also observed a significant excess of genetic markers surpassing P < 1 x 10-6, suggesting that many of them could represent true positive associations with XFS.
Our expanded GWAS conducted on 9,700 XFS cases and 98,000 controls confirmed earlier observations and identified at least four novel genetic loci for XFS. Replication experiments for robust verification of these new findings are now underway. Our findings will broaden current understanding of the disease pathways that underlie XFS.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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