| Literature DB >> 25706626 |
Tin Aung1, Mineo Ozaki2, Takanori Mizoguchi3, R Rand Allingham4, Zheng Li5, Aravind Haripriya6, Satoko Nakano7, Steffen Uebe8, Jeffrey M Harder9, Anita S Y Chan10, Mei Chin Lee11, Kathryn P Burdon12, Yury S Astakhov13, Khaled K Abu-Amero14, Juan C Zenteno15, Yildirim Nilgün16, Tomasz Zarnowski17, Mohammad Pakravan18, Leen Abu Safieh19, Liyun Jia20, Ya Xing Wang21, Susan Williams22, Daniela Paoli23, Patricio G Schlottmann24, Lulin Huang25, Kar Seng Sim5, Jia Nee Foo5, Masakazu Nakano26, Yoko Ikeda27, Rajesh S Kumar28, Morio Ueno27, Shin-ichi Manabe29, Ken Hayashi29, Shigeyasu Kazama30, Ryuichi Ideta31, Yosai Mori32, Kazunori Miyata33, Kazuhisa Sugiyama34, Tomomi Higashide34, Etsuo Chihara35, Kenji Inoue36, Satoshi Ishiko37, Akitoshi Yoshida38, Masahide Yanagi39, Yoshiaki Kiuchi39, Makoto Aihara40, Tsutomu Ohashi41, Toshiya Sakurai42, Takako Sugimoto43, Hideki Chuman43, Fumihiko Matsuda44, Kenji Yamashiro45, Norimoto Gotoh45, Masahiro Miyake46, Sergei Y Astakhov13, Essam A Osman47, Saleh A Al-Obeidan47, Ohoud Owaidhah18, Leyla Al-Jasim18, Sami Al Shahwan18, Rhys A Fogarty48, Paul Leo49, Yaz Yetkin16, Çilingir Oğuz16, Mozhgan Rezaei Kanavi18, Afsaneh Nederi Beni18, Shahin Yazdani18, Evgeny L Akopov13, Kai-Yee Toh5, Gareth R Howell9, Andrew C Orr50, Yufen Goh5, Wee Yang Meah5, Su Qin Peh5, Ewa Kosior-Jarecka17, Urszula Lukasik17, Mandy Krumbiegel8, Eranga N Vithana11, Tien Yin Wong51, Yutao Liu52, Allison E Ashley Koch53, Pratap Challa4, Robyn M Rautenbach54, David A Mackey55, Alex W Hewitt56, Paul Mitchell57, Jie Jin Wang57, Ari Ziskind54, Trevor Carmichael22, Rangappa Ramakrishnan6, Kalpana Narendran6, Rangaraj Venkatesh6, Saravanan Vijayan58, Peiquan Zhao59, Xueyi Chen60, Dalia Guadarrama-Vallejo15, Ching Yu Cheng61, Shamira A Perera10, Rahat Husain10, Su-Ling Ho62, Ulrich-Christoph Welge-Luessen63, Christian Mardin63, Ursula Schloetzer-Schrehardt63, Axel M Hillmer64, Stefan Herms65, Susanne Moebus66, Markus M Nöthen67, Nicole Weisschuh68, Rohit Shetty28, Arkasubhra Ghosh69, Yik Ying Teo70, Matthew A Brown49, Ignacio Lischinsky71, Jonathan G Crowston72, Michael Coote72, Bowen Zhao19, Jinghong Sang20, Nihong Zhang20, Qisheng You21, Vera Vysochinskaya73, Panayiota Founti74, Anthoula Chatzikyriakidou75, Alexandros Lambropoulos75, Eleftherios Anastasopoulos74, Anne L Coleman76, M Roy Wilson77, Douglas J Rhee78, Jae Hee Kang79, Inna May-Bolchakova80, Steffen Heegaard81, Kazuhiko Mori26, Wallace L M Alward82, Jost B Jonas83, Liang Xu21, Jeffrey M Liebmann84, Balram Chowbay85, Elke Schaeffeler86, Matthias Schwab87, Fabian Lerner88, Ningli Wang20, Zhenglin Yang25, Paolo Frezzotti89, Shigeru Kinoshita27, John H Fingert82, Masaru Inatani90, Kei Tashiro26, André Reis8, Deepak P Edward91, Louis R Pasquale92, Toshiaki Kubota7, Janey L Wiggs78, Francesca Pasutto8, Fotis Topouzis74, Michael Dubina93, Jamie E Craig48, Nagahisa Yoshimura45, Periasamy Sundaresan58, Simon W M John9, Robert Ritch94, Michael A Hauser95, Chiea-Chuen Khor96.
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.Entities:
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Year: 2015 PMID： 25706626 PMCID： PMC4605818 DOI： 10.1038/ng.3226
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330