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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-04

AUTHORS

Tin Aung, 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 Jia, Ya 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, Hideki Chuman, Fumihiko Matsuda, Kenji Yamashiro, Norimoto Gotoh, Masahiro Miyake, Sergei Y Astakhov, Essam A Osman, Saleh A Al-Obeidan, Ohoud Owaidhah, Leyla Al-Jasim, Sami Al Shahwan, Rhys A Fogarty, Paul Leo, Yaz Yetkin, Çilingir Oğuz, Mozhgan Rezaei Kanavi, Afsaneh Naderi Beni, Shahin Yazdani, Evgeny L Akopov, Kai-Yee Toh, Gareth R Howell, Andrew C Orr, Yufen Goh, Wee Yang Meah, Su Qin Peh, Ewa Kosior-Jarecka, Urszula Lukasik, Mandy Krumbiegel, Eranga N Vithana, Tien Yin Wong, Yutao Liu, Allison E Ashley Koch, Pratap Challa, Robyn M Rautenbach, David A Mackey, Alex W Hewitt, Paul Mitchell, Jie Jin Wang, Ari Ziskind, Trevor Carmichael, Rangappa Ramakrishnan, Kalpana Narendran, Rangaraj Venkatesh, Saravanan Vijayan, Peiquan Zhao, Xueyi Chen, Dalia Guadarrama-Vallejo, Ching Yu Cheng, Shamira A Perera, Rahat Husain, Su-Ling Ho, Ulrich-Christoph Welge-Luessen, Christian Mardin, Ursula Schloetzer-Schrehardt, Axel M Hillmer, Stefan Herms, Susanne Moebus, Markus M Nöthen, Nicole Weisschuh, Rohit Shetty, Arkasubhra Ghosh, Yik Ying Teo, Matthew A Brown, Ignacio Lischinsky, Blue Mountains Eye Study GWAS Team, Wellcome Trust Case Control Consortium, Jonathan G Crowston, Michael Coote, Bowen Zhao, Jinghong Sang, Nihong Zhang, Qisheng You, Vera Vysochinskaya, Panayiota Founti, Anthoula Chatzikyriakidou, Alexandros Lambropoulos, Eleftherios Anastasopoulos, Anne L Coleman, M Roy Wilson, Douglas J Rhee, Jae Hee Kang, Inna May-Bolchakova, Steffen Heegaard, Kazuhiko Mori, Wallace L M Alward, Jost B Jonas, Liang Xu, Jeffrey M Liebmann, Balram Chowbay, Elke Schaeffeler, Matthias Schwab, Fabian Lerner, Ningli Wang, Zhenglin Yang, Paolo Frezzotti, Shigeru Kinoshita, John H Fingert, Masaru Inatani, Kei Tashiro, André Reis, Deepak P Edward, Louis R Pasquale, Toshiaki Kubota, Janey L Wiggs, Francesca Pasutto, Fotis Topouzis, Michael Dubina, Jamie E Craig, Nagahisa Yoshimura, Periasamy Sundaresan, Simon W M John, Robert Ritch, Michael A Hauser, Chiea-Chuen Khor

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. More... »

PAGES

387-392

Journal

TITLE

Nature Genetics

ISSUE

4

VOLUME

47

Author Affiliations

  • Genome Institute of Singapore
  • Hayashi Eye Hospital
  • Duke University
  • Aravind Eye Hospital
  • Oita University
  • Jackson Laboratory
  • Singapore National Eye Center
  • Singapore Eye Research Institute
  • University of Tasmania
  • First Pavlov State Medical University of St. Peterburg
  • King Saud University
  • National Autonomous University of Mexico
  • Eskişehir Osmangazi University
  • Medical University of Lublin
  • Shahid Beheshti University of Medical Sciences
  • King Khaled Eye Specialist Hospital
  • Capital Medical University
  • University of the Witwatersrand
  • Chinese Academy of Sciences
  • Kyoto Prefectural University of Medicine
  • Ideta Eye Hospital
  • Miyata Eye Hospital
  • University of Miyazaki
  • Kanazawa University
  • Inouye Eye Hospital
  • Asahikawa Medical University
  • Hiroshima University
  • Kyoto University
  • Flinders University
  • Dalhousie University
  • National University of Singapore
  • Augusta University
  • Duke Medical Center
  • Stellenbosch University
  • University of Melbourne
  • University of Sydney
  • XinHua Hospital
  • First Affiliated Hospital of Xinjiang Medical University
  • Tan Tock Seng Hospital
  • University of Erlangen-Nuremberg
  • University of Basel
  • University of Bonn
  • Universitätsklinikum Tübingen
  • Saint Petersburg Academic University
  • Aristotle University of Thessaloniki
  • University of California Los Angeles
  • Wayne State University
  • Harvard University
  • Brigham and Women's Hospital
  • Rigshospitalet
  • University of Iowa
  • Heidelberg University
  • New York University
  • National Cancer Centre Singapore
  • Robert Bosch Stiftung
  • German Cancer Research Center
  • University of Siena
  • University of Fukui
  • Johns Hopkins University
  • Mount Sinai Hospital
  • From Grant

  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3226

    DOI

    http://dx.doi.org/10.1038/ng.3226

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1026616396

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25706626


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    58 schema:description 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.
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