A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome
Research output: Contribution to journal › Letter › Research › peer-review
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: ORA allele = 9.87, P = 2.13 × 10−217; non-Japanese: ORA 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.
Original language | English |
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Journal | Nature Genetics |
Volume | 47 |
Issue number | 4 |
Pages (from-to) | 387-392 |
Number of pages | 6 |
ISSN | 1061-4036 |
DOIs | |
Publication status | Published - Apr 2015 |
ID: 160925583