@article {382391, title = {A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome.}, journal = {Nat Genet}, volume = {47}, number = {4}, year = {2015}, month = {2015 Apr}, pages = {387-92}, 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 {\texttimes} 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 {\texttimes} 10(-217); non-Japanese: ORA allele = 0.49, P = 2.35 {\texttimes} 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.}, issn = {1546-1718}, doi = {10.1038/ng.3226}, author = {Aung, Tin and Ozaki, Mineo and Mizoguchi, Takanori and Allingham, R Rand and Li, Zheng and Haripriya, Aravind and Nakano, Satoko and Uebe, Steffen and Harder, Jeffrey M and Chan, Anita S Y and Lee, Mei Chin and Burdon, Kathryn P and Astakhov, Yury S and Abu-Amero, Khaled K and Zenteno, Juan C and Nilg{\"u}n, Yildirim and Zarnowski, Tomasz and Pakravan, Mohammad and Safieh, Leen Abu and Jia, Liyun and Wang, Ya Xing and Williams, Susan and Paoli, Daniela and Schlottmann, Patricio G and Huang, Lulin and Sim, Kar Seng and Foo, Jia Nee and Nakano, Masakazu and Ikeda, Yoko and Kumar, Rajesh S and Ueno, Morio and Manabe, Shin-Ichi and Hayashi, Ken and Kazama, Shigeyasu and Ideta, Ryuichi and Mori, Yosai and Miyata, Kazunori and Sugiyama, Kazuhisa and Higashide, Tomomi and Chihara, Etsuo and Inoue, Kenji and Ishiko, Satoshi and Yoshida, Akitoshi and Yanagi, Masahide and Kiuchi, Yoshiaki and Aihara, Makoto and Ohashi, Tsutomu and Sakurai, Toshiya and Sugimoto, Takako and Chuman, Hideki and Matsuda, Fumihiko and Yamashiro, Kenji and Gotoh, Norimoto and Miyake, Masahiro and Astakhov, Sergei Y and Osman, Essam A and Al-Obeidan, Saleh A and Owaidhah, Ohoud and Al-Jasim, Leyla and Shahwan, Sami Al and Fogarty, Rhys A and Leo, Paul and Yetkin, Yaz and O{\u g}uz, {\c C}ilingir and Kanavi, Mozhgan Rezaei and Beni, Afsaneh Nederi and Yazdani, Shahin and Akopov, Evgeny L and Toh, Kai-Yee and Howell, Gareth R and Orr, Andrew C and Goh, Yufen and Meah, Wee Yang and Peh, Su Qin and Kosior-Jarecka, Ewa and Lukasik, Urszula and Krumbiegel, Mandy and Vithana, Eranga N and Wong, Tien Yin and Liu, Yutao and Koch, Allison E Ashley and Challa, Pratap and Rautenbach, Robyn M and Mackey, David A and Hewitt, Alex W and Mitchell, Paul and Wang, Jie Jin and Ziskind, Ari and Carmichael, Trevor and Ramakrishnan, Rangappa and Narendran, Kalpana and Venkatesh, Rangaraj and Vijayan, Saravanan and Zhao, Peiquan and Chen, Xueyi and Guadarrama-Vallejo, Dalia and Cheng, Ching Yu and Perera, Shamira A and Husain, Rahat and Ho, Su-Ling and Welge-Luessen, Ulrich-Christoph and Mardin, Christian and Schloetzer-Schrehardt, Ursula and Hillmer, Axel M and Herms, Stefan and Moebus, Susanne and N{\"o}then, Markus M and Weisschuh, Nicole and Shetty, Rohit and Ghosh, Arkasubhra and Teo, Yik Ying and Brown, Matthew A and Lischinsky, Ignacio and Blue Mountains Eye Study GWAS Team and Wellcome Trust Case Control Consortium 2 and Crowston, Jonathan G and Coote, Michael and Zhao, Bowen and Sang, Jinghong and Zhang, Nihong and You, Qisheng and Vysochinskaya, Vera and Founti, Panayiota and Chatzikyriakidou, Anthoula and Lambropoulos, Alexandros and Anastasopoulos, Eleftherios and Coleman, Anne L and Wilson, M Roy and Rhee, Douglas J and Kang, Jae Hee and May-Bolchakova, Inna and Heegaard, Steffen and Mori, Kazuhiko and Alward, Wallace L M and Jonas, Jost B and Xu, Liang and Liebmann, Jeffrey M and Chowbay, Balram and Schaeffeler, Elke and Schwab, Matthias and Lerner, Fabian and Wang, Ningli and Yang, Zhenglin and Frezzotti, Paolo and Kinoshita, Shigeru and Fingert, John H and Inatani, Masaru and Tashiro, Kei and Reis, Andr{\'e} and Edward, Deepak P and Pasquale, Louis R and Kubota, Toshiaki and Wiggs, Janey L and Pasutto, Francesca and Topouzis, Fotis and Dubina, Michael and Craig, Jamie E and Yoshimura, Nagahisa and Sundaresan, Periasamy and John, Simon W M and Ritch, Robert and Hauser, Michael A and Khor, Chiea-Chuen} }