Title
A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome.
Document Type
Article
Publication Date
4-2015
JAX Source
Nat Genet 2015 Apr; 47(4):387-92.
Volume
47
Issue
4
First Page
387
Last Page
392
ISSN
1546-1718
PMID
25706626
Grant
EY11721
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: 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. Nat Genet 2015 Apr; 47(4):387-92.
Recommended Citation
Aung T,
Ozaki M,
Mizoguchi T,
Allingham R,
Li Z,
Haripriya A,
Nakano S,
Uebe S,
Harder JM,
Chan A,
Lee M,
Burdon K,
Astakhov Y,
Abu-Amero K,
Zenteno J,
Nilgün Y,
Zarnowski T,
Pakravan M,
Safieh L,
Jia L,
Wang Y,
Williams S,
Paoli D,
Schlottmann P,
Huang L,
Sim K,
Foo J,
Nakano M,
Ikeda Y,
Kumar R,
Ueno M,
Manabe S,
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 S,
Osman E,
Al-Obeidan S,
Owaidhah O,
Al-Jasim L,
Shahwan S,
Fogarty R,
Leo P,
Yetkin Y,
Oğuz Ç,
Kanavi M,
Beni A,
Yazdani S,
Akopov E,
Toh K,
Howell GR,
Orr A,
Goh Y,
Meah W,
Peh S,
Kosior-Jarecka E,
Lukasik U,
Krumbiegel M,
Vithana E,
Wong T,
Liu Y,
Koch A,
Challa P,
Rautenbach R,
Mackey D,
Hewitt A,
Mitchell P,
Wang J,
Ziskind A,
Carmichael T,
Ramakrishnan R,
Narendran K,
Venkatesh R,
Vijayan S,
Zhao P,
Chen X,
Guadarrama-Vallejo D,
Cheng C,
Perera S,
Husain R,
Ho S,
Welge-Luessen U,
Mardin C,
Schloetzer-Schrehardt U,
Hillmer A,
Herms S,
Moebus S,
Nöthen M,
Weisschuh N,
Shetty R,
Ghosh A,
Teo Y,
Brown M,
Lischinsky I,
Crowston J,
Coote M,
Zhao B,
Sang J,
Zhang N,
You Q,
Vysochinskaya V,
Founti P,
Chatzikyriakidou A,
Lambropoulos A,
Anastasopoulos E,
Coleman A,
Wilson M,
Rhee D,
Kang J,
May-Bolchakova I,
Heegaard S,
Mori K,
Alward W,
Jonas J,
Xu L,
Liebmann J,
Chowbay B,
Schaeffeler E,
Schwab M,
Lerner F,
Wang N,
Yang Z,
Frezzotti P,
Kinoshita S,
Fingert J,
Inatani M,
Tashiro K,
Reis A,
Edward D,
Pasquale L,
Kubota T,
Wiggs J,
Pasutto F,
Topouzis F,
Dubina M,
Craig J,
Yoshimura N,
Sundaresan P,
John SW,
Ritch R,
Hauser M,
Khor C.
A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome. Nat Genet 2015 Apr; 47(4):387-92.