A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome Academic Article uri icon

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.

authors

  • Coote, Michael
  • Aung, T
  • Ozaki, M
  • Mizoguchi, T
  • Allingham, RR
  • Li, Z
  • Haripriya, A
  • Nakano, S
  • Uebe, S
  • Harder, JM
  • Chan, ASY
  • Lee, MC
  • Burdon, KP
  • Astakhov, YS
  • Abu-Amero, KK
  • Zenteno, JC
  • Nilgün, Y
  • Zarnowski, T
  • Pakravan, M
  • Safieh, LA
  • Jia, L
  • Wang, YX
  • Williams, S
  • Paoli, D
  • Schlottmann, PG
  • Huang, L
  • Sim, KS
  • Foo, JN
  • Nakano, M
  • Ikeda, Y
  • Kumar, RS
  • Ueno, M
  • Manabe, SI
  • Hayashi, K
  • Kazama, S
  • Ideta, R
  • Mori, Y
  • Miyata, K
  • Sugiyama, K
  • Higashide, T
  • Chihara, E
  • Inoue, K
  • Ishiko, S
  • Yoshida, A
  • Yanagi, M
  • Kiuchi, Y
  • Aihara, M
  • Ohashi, T
  • Sakurai, T
  • Sugimoto, T
  • Chuman, H
  • Matsuda, F
  • Yamashiro, K
  • Gotoh, N
  • Miyake, M
  • Astakhov, SY
  • Osman, EA
  • Al-Obeidan, SA
  • Owaidhah, O
  • Al-Jasim, L
  • Shahwan, SA
  • Fogarty, RA
  • Leo, P
  • Yetkin, Y
  • Ouz, Ç
  • Kanavi, MR
  • Beni, AN
  • Yazdani, S
  • Akopov, EL
  • Toh, KY
  • Howell, GR
  • Orr, AC
  • Goh, Y
  • Meah, WY
  • Peh, SQ
  • Kosior-Jarecka, E
  • Lukasik, U
  • Krumbiegel, M
  • Vithana, EN
  • Wong, TY
  • Liu, Y

publication date

  • 2015

has subject area