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.
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, Tin; Ozaki, Mineo; Mizoguchi, Takanori; Allingham, R Rand; Li, Zheng; Haripriya, Aravind; Nakano, Satoko; Uebe, Steffen; Harder, Jeffrey M.; Chan, Anita S Y; Lee, Mei Chin; Burdon, Kathryn P; Astakhov, Yury S; Abu-Amero, Khaled K; Zenteno, Juan C; Nilgün, Yildirim; Zarnowski, Tomasz; Pakravan, Mohammad; Safieh, Leen Abu; Jia, Liyun; Wang, Ya Xing; Williams, Susan; Paoli, Daniela; Schlottmann, Patricio G; Huang, Lulin; Sim, Kar Seng; Foo, Jia Nee; Nakano, Masakazu; Ikeda, Yoko; Kumar, Rajesh S; Ueno, Morio; Manabe, Shin-Ichi; Hayashi, Ken; Kazama, Shigeyasu; Ideta, Ryuichi; Mori, Yosai; Miyata, Kazunori; Sugiyama, Kazuhisa; Higashide, Tomomi; Chihara, Etsuo; Inoue, Kenji; Ishiko, Satoshi; Yoshida, Akitoshi; Yanagi, Masahide; Kiuchi, Yoshiaki; Aihara, Makoto; Ohashi, Tsutomu; Sakurai, Toshiya; Sugimoto, Takako; Chuman, Hideki; Matsuda, Fumihiko; Yamashiro, Kenji; Gotoh, Norimoto; Miyake, Masahiro; Astakhov, Sergei Y; Osman, Essam A; Al-Obeidan, Saleh A; Owaidhah, Ohoud; Al-Jasim, Leyla; Shahwan, Sami Al; Fogarty, Rhys A; Leo, Paul; Yetkin, Yaz; Oğuz, Çilingir; Kanavi, Mozhgan Rezaei; Beni, Afsaneh Nederi; Yazdani, Shahin; Akopov, Evgeny L; Toh, Kai-Yee; Howell, Gareth R.; Orr, Andrew C; Goh, Yufen; Meah, Wee Yang; Peh, Su Qin; Kosior-Jarecka, Ewa; Lukasik, Urszula; Krumbiegel, Mandy; Vithana, Eranga N; Wong, Tien Yin; Liu, Yutao; Koch, Allison E Ashley; Challa, Pratap; Rautenbach, Robyn M; Mackey, David A; Hewitt, Alex W; Mitchell, Paul; Wang, Jie Jin; Ziskind, Ari; Carmichael, Trevor; Ramakrishnan, Rangappa; Narendran, Kalpana; Venkatesh, Rangaraj; Vijayan, Saravanan; Zhao, Peiquan; Chen, Xueyi; Guadarrama-Vallejo, Dalia; Cheng, Ching Yu; Perera, Shamira A; Husain, Rahat; Ho, Su-Ling; Welge-Luessen, Ulrich-Christoph; Mardin, Christian; Schloetzer-Schrehardt, Ursula; Hillmer, Axel M; Herms, Stefan; Moebus, Susanne; Nöthen, Markus M; Weisschuh, Nicole; Shetty, Rohit; Ghosh, Arkasubhra; Teo, Yik Ying; Brown, Matthew A; Lischinsky, Ignacio; Crowston, Jonathan G; Coote, Michael; Zhao, Bowen; Sang, Jinghong; Zhang, Nihong; You, Qisheng; Vysochinskaya, Vera; Founti, Panayiota; Chatzikyriakidou, Anthoula; Lambropoulos, Alexandros; Anastasopoulos, Eleftherios; Coleman, Anne L; Wilson, M Roy; Rhee, Douglas J; Kang, Jae Hee; May-Bolchakova, Inna; Heegaard, Steffen; Mori, Kazuhiko; Alward, Wallace L M; Jonas, Jost B; Xu, Liang; Liebmann, Jeffrey M; Chowbay, Balram; Schaeffeler, Elke; Schwab, Matthias; Lerner, Fabian; Wang, Ningli; Yang, Zhenglin; Frezzotti, Paolo; Kinoshita, Shigeru; Fingert, John H; Inatani, Masaru; Tashiro, Kei; Reis, André; Edward, Deepak P; Pasquale, Louis R; Kubota, Toshiaki; Wiggs, Janey L; Pasutto, Francesca; Topouzis, Fotis; Dubina, Michael; Craig, Jamie E; Yoshimura, Nagahisa; Sundaresan, Periasamy; John, Simon W M; Ritch, Robert; Hauser, Michael A; and Khor, Chiea-Chuen, "A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome." (2015). Faculty Research 2015. 61.
https://mouseion.jax.org/stfb2015/61