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

Tin Aung (Lead / Corresponding author), Mineo Ozaki, Takanori Mizoguchi, R. Rand Allingham, Zheng Li, Aravind Haripriya, Satoko Nakano, Steffen Uebe, Jeffrey M. Harder, Anita S. Y. Chan, Mei Chin Lee, Kathryn P. Burdon, Yury S. Astakhov, Khaled K. Abu-Amero, Juan C. Zenteno, Yildirim Nilgün, Tomasz Zarnowski, Mohammad Pakravan, Leen Abu Safieh, Liyun JiaYa Xing Wang, Susan Williams, Daniela Paoli, Patricio G. Schlottmann, Lulin Huang, Kar Seng Sim, Jia Nee Foo, Masakazu Nakano, Yoko Ikeda, Rajesh S. Kumar, Morio Ueno, Shin-ichi Manabe, Ken Hayashi, Shigeyasu Kazama, Ryuichi Ideta, Yosai Mori, Kazunori Miyata, Kazuhisa Sugiyama, Tomomi Higashide, Etsuo Chihara, Kenji Inoue, Satoshi Ishiko, Akitoshi Yoshida, Masahide Yanagi, Yoshiaki Kiuchi, Makoto Aihara, Tsutomu Ohashi, Toshiya Sakurai, Takako Sugimoto, Wellcome Trust Case Control Consortium 2

    Research output: Contribution to journalLetterpeer-review

    89 Citations (Scopus)


    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.

    Original languageEnglish
    Pages (from-to)387-392
    Number of pages6
    JournalNature Genetics
    Issue number4
    Publication statusPublished - Apr 2015


    • 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


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