A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome.
Title | A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Aung, T., Ozaki M., Mizoguchi T., R Allingham R., Li Z., Haripriya A., et al. |
Corporate Authors | Blue Mountains Eye Study GWAS Team, & Wellcome Trust Case Control Consortium 2 |
Journal | Nat Genet |
Volume | 47 |
Issue | 4 |
Pagination | 387-92 |
Date Published | 2015 Apr |
ISSN | 1546-1718 |
Keywords | Animals, Asian Continental Ancestry Group, Calcium Channels, Case-Control Studies, Chromosome Mapping, Exfoliation Syndrome, Genetic Predisposition to Disease, Genome-Wide Association Study, Glaucoma, Open-Angle, HEK293 Cells, HeLa Cells, Humans, Japan, MCF-7 Cells, Mice, Mice, Inbred C57BL, Polymorphism, Single Nucleotide, Tumor Cells, Cultured |
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. |
DOI | 10.1038/ng.3226 |
Alternate Journal | Nat Genet |
PubMed ID | 25706626 |
PubMed Central ID | PMC4605818 |
Grant List | R01 EY011721 / EY / NEI NIH HHS / United States R29 EY011721 / EY / NEI NIH HHS / United States EY018825 / EY / NEI NIH HHS / United States 085475/08/Z / / Wellcome Trust / United Kingdom R01 EY018825 / EY / NEI NIH HHS / United States EY023512 / EY / NEI NIH HHS / United States R01 EY020928 / EY / NEI NIH HHS / United States / / Howard Hughes Medical Institute / United States 085475/B/08/Z / / Wellcome Trust / United Kingdom P30 EY014104 / EY / NEI NIH HHS / United States EY11721 / EY / NEI NIH HHS / United States R01 EY023512 / EY / NEI NIH HHS / United States R01 EY013882 / EY / NEI NIH HHS / United States |