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Updated: Apr 17, 2026
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome
Tin Aung1, Mineo Ozaki2, Takanori Mizoguchi3
11] Singapore Eye Research Institute, Singapore. [2] Singapore National Eye Center, Singapore. [3] Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. [4] Division of Human Genetics, Genome Institute of Singapore, Singapore. [5] Duke University-National University of Singapore Graduate Medical School, Singapore.
Abstract:
Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) of 1,484 cases and 1,188 controls from Japan and followed up the most significant findings in a further 6,901 cases and 20,727 controls from 17 countries across 6 continents. We discovered a genome-wide significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (odds ratio (OR) = 1.16, P = 3.36 × 10(-11)). Although we also confirmed overwhelming association at the LOXL1 locus, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on the ancestry group (Japanese: OR(A allele) = 9.87, P = 2.13 × 10(-217); non-Japanese: OR(A allele) = 0.49, P = 2.35 × 10(-31)). Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease.
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