Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-07

AUTHORS

Tin Aung, Mineo Ozaki, Mei Chin Lee, Ursula Schlötzer-Schrehardt, Gudmar Thorleifsson, Takanori Mizoguchi, Robert P Igo, Aravind Haripriya, Susan E Williams, Yury S Astakhov, Andrew C Orr, Kathryn P Burdon, Satoko Nakano, Kazuhiko Mori, Khaled Abu-Amero, Michael Hauser, Zheng Li, Gopalakrishnan Prakadeeswari, Jessica N Cooke Bailey, Alina Popa Cherecheanu, Jae H Kang, Sarah Nelson, Ken Hayashi, Shin-ichi Manabe, Shigeyasu Kazama, Tomasz Zarnowski, Kenji Inoue, Murat Irkec, Miguel Coca-Prados, Kazuhisa Sugiyama, Irma Järvelä, Patricio Schlottmann, S Fabian Lerner, Hasnaa Lamari, Yildirim Nilgün, Mukharram Bikbov, Ki Ho Park, Soon Cheol Cha, Kenji Yamashiro, Juan C Zenteno, Jost B Jonas, Rajesh S Kumar, Shamira A Perera, Anita S Y Chan, Nino Kobakhidze, Ronnie George, Lingam Vijaya, Tan Do, Deepak P Edward, Lourdes de Juan Marcos, Mohammad Pakravan, Sasan Moghimi, Ryuichi Ideta, Daniella Bach-Holm, Per Kappelgaard, Barbara Wirostko, Samuel Thomas, Daniel Gaston, Karen Bedard, Wenda L Greer, Zhenglin Yang, Xueyi Chen, Lulin Huang, Jinghong Sang, Hongyan Jia, Liyun Jia, Chunyan Qiao, Hui Zhang, Xuyang Liu, Bowen Zhao, Ya-Xing Wang, Liang Xu, Stéphanie Leruez, Pascal Reynier, George Chichua, Sergo Tabagari, Steffen Uebe, Matthias Zenkel, Daniel Berner, Georg Mossböck, Nicole Weisschuh, Ursula Hoja, Ulrich-Christoph Welge-Luessen, Christian Mardin, Panayiota Founti, Anthi Chatzikyriakidou, Theofanis Pappas, Eleftherios Anastasopoulos, Alexandros Lambropoulos, Arkasubhra Ghosh, Rohit Shetty, Natalia Porporato, Vijayan Saravanan, Rengaraj Venkatesh, Chandrashekaran Shivkumar, Narendran Kalpana, Sripriya Sarangapani, Mozhgan R Kanavi, Afsaneh Naderi Beni, Shahin Yazdani, Alireza lashay, Homa Naderifar, Nassim Khatibi, Antonio Fea, Carlo Lavia, Laura Dallorto, Teresa Rolle, Paolo Frezzotti, Daniela Paoli, Erika Salvi, Paolo Manunta, Yosai Mori, Kazunori Miyata, Tomomi Higashide, Etsuo Chihara, Satoshi Ishiko, Akitoshi Yoshida, Masahide Yanagi, Yoshiaki Kiuchi, Tsutomu Ohashi, Toshiya Sakurai, Takako Sugimoto, Hideki Chuman, Makoto Aihara, Masaru Inatani, Masahiro Miyake, Norimoto Gotoh, Fumihiko Matsuda, Nagahisa Yoshimura, Yoko Ikeda, Morio Ueno, Chie Sotozono, Jin Wook Jeoung, Min Sagong, Kyu Hyung Park, Jeeyun Ahn, Marisa Cruz-Aguilar, Sidi M Ezzouhairi, Abderrahman Rafei, Yaan Fun Chong, Xiao Yu Ng, Shuang Ru Goh, Yueming Chen, Victor H K Yong, Muhammad Imran Khan, Olusola O Olawoye, Adeyinka O Ashaye, Idakwo Ugbede, Adeola Onakoya, Nkiru Kizor-Akaraiwe, Chaiwat Teekhasaenee, Yanin Suwan, Wasu Supakontanasan, Suhanya Okeke, Nkechi J Uche, Ifeoma Asimadu, Humaira Ayub, Farah Akhtar, Ewa Kosior-Jarecka, Urszula Lukasik, Ignacio Lischinsky, Vania Castro, Rodolfo Perez Grossmann, Gordana Sunaric Megevand, Sylvain Roy, Edward Dervan, Eoin Silke, Aparna Rao, Priti Sahay, Pablo Fornero, Osvaldo Cuello, Delia Sivori, Tamara Zompa, Richard A Mills, Emmanuelle Souzeau, Paul Mitchell, Jie Jin Wang, Alex W Hewitt, Michael Coote, Jonathan G Crowston, Sergei Y Astakhov, Eugeny L Akopov, Anton Emelyanov, Vera Vysochinskaya, Gyulli Kazakbaeva, Rinat Fayzrakhmanov, Saleh A Al-Obeidan, Ohoud Owaidhah, Leyla Ali Aljasim, Balram Chowbay, Jia Nee Foo, Raphael Q Soh, Kar Seng Sim, Zhicheng Xie, Augustine W O Cheong, Shi Qi Mok, Hui Meng Soo, Xiao Yin Chen, Su Qin Peh, Khai Koon Heng, Rahat Husain, Su-Ling Ho, Axel M Hillmer, Ching-Yu Cheng, Francisco A Escudero-Domínguez, Rogelio González-Sarmiento, Frederico Martinon-Torres, Antonio Salas, Kessara Pathanapitoon, Linda Hansapinyo, Boonsong Wanichwecharugruang, Naris Kitnarong, Anavaj Sakuntabhai, Hip X Nguyn, Giang T T Nguyn, Trình V Nguyn, Werner Zenz, Alexander Binder, Daniela S Klobassa, Martin L Hibberd, Sonia Davila, Stefan Herms, Markus M Nöthen, Susanne Moebus, Robyn M Rautenbach, Ari Ziskind, Trevor R Carmichael, Michele Ramsay, Lydia Álvarez, Montserrat García, Héctor González-Iglesias, Pedro P Rodríguez-Calvo, Luis Fernández-Vega Cueto, Çilingir Oguz, Nevbahar Tamcelik, Eray Atalay, Bilge Batu, Dilek Aktas, Burcu Kasım, M Roy Wilson, Anne L Coleman, Yutao Liu, Pratap Challa, Leon Herndon, Rachel W Kuchtey, John Kuchtey, Karen Curtin, Craig J Chaya, Alan Crandall, Linda M Zangwill, Tien Yin Wong, Masakazu Nakano, Shigeru Kinoshita, Anneke I den Hollander, Eija Vesti, John H Fingert, Richard K Lee, Arthur J Sit, Bradford J Shingleton, Ningli Wang, Daniele Cusi, Raheel Qamar, Peter Kraft, Margaret A Pericak-Vance, Soumya Raychaudhuri, Steffen Heegaard, Tero Kivelä, André Reis, Friedrich E Kruse, Robert N Weinreb, Louis R Pasquale, Jonathan L Haines, Unnur Thorsteinsdottir, Fridbert Jonasson, R Rand Allingham, Dan Milea, Robert Ritch, Toshiaki Kubota, Kei Tashiro, Eranga N Vithana, Shazia Micheal, Fotis Topouzis, Jamie E Craig, Michael Dubina, Periasamy Sundaresan, Kari Stefansson, Janey L Wiggs, Francesca Pasutto, Chiea Chuen Khor

ABSTRACT

Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 × 10-14) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10-8). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology. More... »

PAGES

993

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    7

    VOLUME

    49

    Author Affiliations

  • National University of Singapore
  • University of Miyazaki
  • Duke NUS Graduate Medical School
  • deCODE Genetics (Iceland)
  • Case Western Reserve University
  • Aravind Eye Hospital
  • University of the Witwatersrand
  • First Pavlov State Medical University of St. Peterburg
  • Dalhousie University
  • University of Tasmania
  • Oita University
  • Kyoto Prefectural University of Medicine
  • King Saud University
  • Duke Medical Center
  • Genome Institute of Singapore
  • Clinical Emergency Hospital Bucharest
  • University of Washington
  • Hayashi Eye Hospital
  • Medical University of Lublin
  • Hacettepe University
  • Yale University
  • Kanazawa University
  • University of Helsinki
  • Eskişehir Osmangazi University
  • Ufa Eye Research Institute
  • Yeungnam University
  • Otsu Red Cross Hospital
  • National Autonomous University of Mexico
  • Capital Medical University
  • Narayana Nethralaya
  • Singapore National Eye Center
  • Sankara Nethralaya
  • University of Illinois at Chicago
  • Instituto de Investigación Biomédica de Salamanca
  • Shahid Beheshti University of Medical Sciences
  • Tehran University of Medical Sciences
  • Ideta Eye Hospital
  • University of Utah
  • University of Electronic Science and Technology of China
  • First Affiliated Hospital of Xinjiang Medical University
  • Chinese Academy of Sciences
  • Jinan University
  • Centre Hospitalier Universitaire de Angers
  • David Tvildiani Medical University
  • University of Erlangen-Nuremberg
  • Medical University of Graz
  • Aristotle University of Thessaloniki
  • University of Turin
  • University of Siena
  • University of Milan
  • Vita-Salute San Raffaele University
  • Miyata Eye Hospital
  • Asahikawa Medical University
  • Hiroshima University
  • University of Tokyo
  • University of Fukui
  • Kyoto University
  • Kitano Hospital
  • Seoul National University Bundang Hospital
  • Boramae Medical Center
  • Singapore Eye Research Institute
  • Radboud University Nijmegen Medical Centre
  • University College Hospital, Ibadan
  • Lagos University Teaching Hospital
  • University of Nigeria, Nsukka
  • COMSATS Institute of Information Technology
  • Cayetano Heredia University
  • Mater Misericordiae University Hospital
  • L V Prasad Eye Institute
  • Servicio Diabetología Hospital Córdoba
  • Flinders University
  • University of Sydney
  • University of Melbourne
  • Saint Petersburg Academic University
  • King Khaled Eye Specialist Hospital
  • Nanyang Technological University
  • Tan Tock Seng Hospital
  • Complejo Hospitalario de Salamanca
  • University of Salamanca
  • Instituto de Investigación Sanitaria de Santiago
  • University of Santiago de Compostela
  • Chiang Mai University
  • Rajavithi Hospital
  • French National Centre for Scientific Research
  • London School of Hygiene & Tropical Medicine
  • University Hospital of Basel
  • University of Bonn
  • Tygerberg Hospital
  • Fernández-Vega Ophthalmological Institute
  • Istanbul University
  • Wayne State University
  • University of California Los Angeles
  • Augusta University
  • Duke University
  • Vanderbilt University Medical Center
  • University of California, San Diego
  • Turku University Hospital
  • University of Iowa
  • University of Miami
  • Mayo Clinic
  • Ophthalmic Consultants of Boston
  • Institute of Biomedical Technologies
  • Isra University
  • Harvard University
  • Karolinska University Hospital
  • Helsinki University Central Hospital
  • University of Iceland
  • National University Hospital of Iceland
  • Mount Sinai Hospital
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3875

    DOI

    http://dx.doi.org/10.1038/ng.3875

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1085707829

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28553957


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