| Title: |
Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci |
| Authors: |
Aung, Tin, P; Ozaki, Mineo; Lee, Mei Chin; Schlötzer-Schrehardt, Ursula; Thorleifsson, Gudmar; Mizoguchi, Takanori; Igo, Robert; Haripriya, Aravind; Williams, Susan; Astakhov, Yury; Orr, Andrew; Burdon, Kathryn; Nakano, Satoko; Mori, Kazuhiko; Abu-Amero, Khaled; Hauser, Michael; Li, Zheng; Prakadeeswari, Gopalakrishnan; Bailey, Jessica; Cherecheanu, Alina Popa; Kang, Jae, H.; Nelson, Sarah; Hayashi, Ken; Manabe, Shin-Ichi; Kazama, Shigeyasu; Zarnowski, Tomasz; Inoue, Ken; Irkec, Murat; Coca-Prados, Miguel; Sugiyama, Kazuhisa; Järvelä, Irma; Schlottmann, Patricio; Lerner, S. Fabian; Lamari, Hasnaa; Nilgün, Yildirim; Bikbov, Mukharram; Park, Ki Ho; Cha, Soon Cheol; Yamashiro, Ken; Zenteno, Juan; Jonas, Jost; Kumar, Rajesh; Perera, Shamira; Cha, Anita; Kobakhidze, Nino; George, Ronnie; Li, Lingam; Do, Tan; Edward, Deepak; de Juan Marcos, Juan; Pakravan, Mohammad; Moghimi, Sasan; Ideta, Ryuichi; Bach-Holm, Daniella; Kappelgaard, Per; Wirostko, Barbara; Thomas, Samuel; Gaston, Daniel; Bedard, Karen; Greer, Wenda; Yang, Zheng; Chen, Xueyi; Huang, Lulin; Sang, Jinghong; Jia, Hongyan; Li, Liyun; Qiao, Chunyan; Zhang, Hui; Li, Xuyang; Zhao, Bowen; Wang, Ya-Xing; Li, Liang; Leruez, Stéphanie; Reynier, Pascal; Chichua, George; Tabagari, Sergo; Uebe, Steffen; Zenkel, Matthias; Berner, Daniel; Mossböck, Georg; Weisschuh, Nicole; Hoja, Ursula; Welge-Luessen, Ulrich-Christoph; Mardin, Christian; Founti, Panayiota; Cha, Anthi; Pappas, Theofanis; Anastasopoulos, Eleftherios; Lambropoulos, Alexandros; Ghosh, Arkasubhra; Shetty, Rohit; Porporato, Natalia; Vijaya, Vijayan; Venkatesh, Rengaraj; Cha, Chandrashekaran; Kalpana, Narendran; Sarangapani, Sripriya; Kanavi, Mozhgan; Beni, Afsaneh Naderi; Yazdani, Shahin; Lashay, Alireza; Naderifar, Homa; Khatibi, Nassim; Fea, Antonio; Lavia, Carlo; Dallorto, Laura; Rolle, Teresa; Frezzotti, Paolo; Paoli, Daniel; Salvi, Erika; Manunta, Paolo; Mori, Yosai; Miyata, Kazunori; Higashide, Tomomi; Chihara, Etsuo; Ishiko, Satoshi; Yoshida, Akitoshi; Yanagi, Masahide; Kiuchi, Yoshiaki; Ohashi, Tsutomu; Sakurai, Toshiya; Sugimoto, Takako; Chuman, Hideki; Aihara, Makoto; Inatani, Masaru; Miyake, Masahiro; Gotoh, Norimoto; Matsuda, Fumihiko; Yoshimura, Nagahisa; Ikeda, Yoko; Mori, Morio; Sotozono, Chie; Jeoung, Jin Wook; Sagong, Min; Park, Kyu Hyung; Ahn, Jeeyun; Cruz-Aguilar, Marisa; Ezzouhairi, Sidi; Rafei, Abderrahman; Chong, Yaan Fun; Ng, Xiao Yu; Goh, Shuang Ru; Chen, Yueming; Yong, Victor; Khan, Muhammad Imran; Olawoye, Olusola; Ashaye, Adeyinka; Ugbede, Idakwo; Onakoya, Adeola; Kizor-Akaraiwe, Nkiru; Cha, Chaiwat; Suwan, Yanin; Supakontanasan, Wasu; Okeke, Suhanya; Uche, Nkechi; Asimadu, Ifeoma; Ayub, Humaira; Akhtar, Farah; Kosior-Jarecka, Ewa; Lukasik, Urszula; Li, Ignacio; Castro, Vania; Grossmann, Per; Megevand, Gordana Sunaric; Roy, Sylvain; Dervan, Edward; Silke, Eoin; Rao, Aparna; Sahay, Priti; Fornero, Pablo; Cuello, Osvaldo; Sivori, Delia; Zompa, Tamara; Mills, Richard; Souzeau, Emmanuelle; Mitchell, Paul; Wang, Jie Jin; Hewitt, Alex; Coote, Michael; Crowston, Jonathan; Astakhov, Sergei; Akopov, Eugeny; Emelyanov, Anton; Vysochinskaya, Vera; Kazakbaeva, Gyulli; Fayzrakhmanov, Rinat; Al-Obeidan, Saleh; Owaidhah, Ohoud; Aljasim, Leyla Ali; Chowbay, Balram; Jia, Jia Nee; Soh, Raphael; Sim, Kar Seng; Xie, Zhicheng; Cheong, Augustine; Mok, Shi Qi; Soo, Hui; Chen, Xiao Yin; Peh, Su Qin; Heng, Khai Koon; Husain, Rahat; Li, Su-Ling; Hillmer, Axel; Chen, Ching-Yu; Do, Francisco; González-Sarmiento, Rogelio; Martinon-Torres, Frederico; Salas, Antonio; Pathanapitoon, Kessara; Wanichwecharugruang, Boonsong; Kitnarong, Naris; Sakuntabhai, Anavaj; Ng, Hip; Ng, Giang; Ng, Trình; Zenz, Werner; Binder, Alex; Klobassa, Daniel; Hibberd, Martin, L; Davila, Sonia; Herms, Stefan; Nöthen, Markus; Moebus, Susan; Rautenbach, Robyn; Ziskind, Ari; Carmichael, Trevor; Ramsay, Michele; Álvarez, Lydia; García, Montserrat; González-Iglesias, Héctor; Rodríguez-Calvo, Pedro; Cueto, Luis Fernández-Vega; Oguz, Çilingir; Tamcelik, Nevbahar; Atalay, Eray; Batu, Bilge; Aktas, Dilek; Kasim, Burcu; Coleman, Anne; Li, Yutao; Cha, Pratap; Herndon, Leon; Kuchtey, Rachel; Kuchtey, John; Curtin, Karen; Cha, Craig; Crandall, Alan; Li, Linda; Wong, Tien Yin; Nakano, Masakazu; Kinoshita, Shigeru; Ho, Anne; Vesti, Eija; Fingert, John; Lee, Richard; Sit, Arthur; Shingleton, Bradford; Wang, Ningli; Cusi, Daniel; Qamar, Raheel; Kraft, Peter; Pericak-Vance, Margaret; Raychaudhuri, Soumya; Heegaard, Steffen; Kivelä, Tero; Reis, André; Kruse, Friedrich; Weinreb, Robert; Pasquale, Louis; Haines, Jonathan, L.; Thorsteinsdóttir, Unnur; Jonasson, Fridbert; Allingham, R Rand; Milea, Dan; Ritch, Robert; Kubota, Toshiaki; Tashiro, Kei; Vithana, Eranga; Micheal, Shazia; Topouzis, Fotis; Craig, Jamie E; Dubina, Michael; Sundaresan, Per; Stefansson, Stefan; Wiggs, Janey; Pasutto, Francesca; Khor, Chiea Chuen |
| Contributors: |
Singapore Eye Research Institute Singapore (SERI); Ozaki Eye Hospital Miyazaki; Friedrich-Alexander Universität Erlangen-Nürnberg = University of Erlangen-Nuremberg (FAU); deCODE genetics Reykjavik; Mizoguchi Eye Hospital Sasebo; Case Western Reserve University Cleveland; Aravind Eye Hospital Madurai, India; University of the Witwatersrand Johannesburg (WITS); Pavlov First Saint Petersburg State Medical University St. Petersburg; Dalhousie University Halifax; Flinders University Adelaide, Australia; Kyoto Prefectural University of Medicine Kyoto, Japon; King Saud University Riyadh (KSU); Genome Institute of Singapore (GIS); Aravind Medical Research Foundation (AMRF); University of Medicine and Pharmacy “Carol Davila” (UMPCD); Harvard Medical School Boston (HMS); University of Washington Seattle; Hayashi Eye Hospital Fukuoka; Shinjo Eye Clinic Nagoya; Medical University of Lublin; Inoue Eye Hospital Tokyo; Hacettepe University = Hacettepe Üniversitesi; Universidad de Oviedo = University of Oviedo; Kanazawa University (KU); Department of Medical and Clinical Genetics Helsinki; Haartman Institute Helsinki; Faculty of Medecine Helsinki; Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine Helsinki; Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki; Organizacion Medica de Investigacion (OMI BUENOS AIRES); Fundacion para el Estudio del Glaucoma Buenos Aires; Chercheur indépendant; Eskisehir Osmangazi University; Ufa Eye Research Institute Bashkortostan; Seoul National University Hospital; Yeungnam University South Korea; Kyōto daigaku = Kyoto University; Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM); Universität Heidelberg Heidelberg = Heidelberg University; Birla Institute of Scientific Research (BISR); B. M. Birla Science and Technology Center; Faculty of Computer Science; Department of Pathology and Immunology; Hôpitaux Universitaires de Genève = University Hospital of Geneva Genève (HUG); Key Laboratory for Information System Security; ministry of education; Numerical modeling and high performance computing for evolution problems in complex domains and heterogeneous media (NACHOS); Centre Inria d'Université Côte d'Azur; Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Alexandre Dieudonné (LJAD); Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UniCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UniCA); Centre Hospitalier Universitaire d'Angers (CHU Angers); Institute of Human Genetics Erlangen, Allemagne; Department of Ophthalmology, School of Medicine Thessaloniki, Grèce; Aristotle University of Thessaloniki; Università degli Studi di Siena = University of Siena (UNISI); Department of Medicine, Surgery, and Dentistry; University of Milano; Japan Advanced Institute of Science and Technology (JAIST); Etudes génomiques trans-ethniques des maladies multifactorielles; Kyōto daigaku = Kyoto University-Institut National de la Santé et de la Recherche Médicale (INSERM); Fondation Ophtalmologique Adolphe de Rothschild Paris; Archaeogenetics Laboratory; Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases; Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS); Rheinische Friedrich-Wilhelms-Universität Bonn; University of Kentucky (UK); Helsinki University Hospital Finland (HUS); COMSATS Institute of Information Technology (CIIT); Department of Epidemiology; Harvard School of Public Health; University of Miami Leonard M. Miller School of Medicine (UMMSM); Brigham and Women's Hospital Boston; Københavns Universitet = University of Copenhagen = Université de Copenhague (UCPH); Helsingin yliopisto = Helsingfors universitet = University of Helsinki; University of California San Diego (UC San Diego); University of California (UC); University of Iceland Reykjavik; New York Eye and Ear Infirmary of Mount Sinai New York (NYEE); Oita University; Radboud University Medical Center Nijmegen (RadboudUMC) |
| Source: |
ISSN: 1061-4036. |
| Publisher Information: |
CCSD; Nature Publishing Group |
| Publication Year: |
2017 |
| Collection: |
Inserm: HAL (Institut national de la santé et de la recherche médicale) |
| Subject Terms: |
[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]; [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]; [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics; [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE]; [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology; [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology; [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie |
| Description: |
International audience ; Exfoliation syndrome (XFS) is the commonest known risk factor for secondary glaucoma and a significant cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A have been previously 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 between populations,and to identify new variants associated with XFS. We identified a rare, protective allele at LOXL1 (p.407Phe, OR= 25, P=2.9 x 10-14) through deep resequencing of XFS cases and controls from 9 countries. This variant results in increased cellular adhesion strength compared to the wild-type (p.407Tyr) allele. 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 x 10-8). Index variants at the new loci map to chromosomes 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/28553957; PUBMED: 28553957 |
| DOI: |
10.1038/ng.3875 |
| Availability: |
https://pasteur.hal.science/pasteur-02003892; https://pasteur.hal.science/pasteur-02003892v1/document; https://pasteur.hal.science/pasteur-02003892v1/file/Aung_Genetic_AM2017.pdf; https://doi.org/10.1038/ng.3875 |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.5DA91B34 |
| Database: |
BASE |