A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome


Creative Commons License

Aung T., Ozaki M., Mizoguchi T., Allingham R. R. , Li Z., Haripriya A., ...Daha Fazla

NATURE GENETICS, cilt.47, sa.4, ss.387-394, 2015 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 47 Konu: 4
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1038/ng.3226
  • Dergi Adı: NATURE GENETICS
  • Sayfa Sayıları: ss.387-394

Özet

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 x 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 x 10(-217); non-Japanese: ORA allele = 0.49, P = 2.35 x 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.