Publication:
Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci

Issued Date

2017-07-01

Resource Type

Article

ISSN

15461718
10614036

DOI

10.1038/ng.3875

Other identifier(s)

2-s2.0-85021706287

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Nature Genetics. Vol.49, No.7 (2017), 993-1004

Suggested Citation

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 Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci. Nature Genetics. Vol.49, No.7 (2017), 993-1004. doi:10.1038/ng.3875 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/41856

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Title

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

Author(s)

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

Other Contributor(s)

Singapore Eye Research Institute
 Singapore National Eye Centre
 Yong Loo Lin School of Medicine
 Ozaki Eye Hospital
 University of Miyazaki
 Duke-NUS Medical School Singapore
 Universitätsklinik Erlangen und Medizinische Fakultät
 deCODE genetics
 Mizoguchi Eye Clinic
 Case Western Reserve University
 Aravind Eye Hospital
 University of Witwatersrand
 Pavlov University
 Dalhousie University
 Flinders University
 University of Tasmania
 Oita University
 Kyoto Prefectural University of Medicine
 King Saud University Medical College
 University of Florida
 Duke University Eye Center
 Duke University Medical Center
 A-Star, Genome Institute of Singapore
 Aravind Medical Research Foundation
 Universitatea de Medicina si Farmacie Carol Davila din Bucuresti
 University Emergency Hospital
 Brigham and Women's Hospital
 University of Washington, Seattle
 Hayashi Eye Hospital
 Shinjo Eye Clinic
 Medical University of Lublin
 Inoue Eye Hospital
 Hacettepe Üniversitesi
 Universidad de Oviedo
 Fernández-Vega Ophthalmological Institute
 Yale University School of Medicine
 Kanazawa University School of Medicine
 Helsingin Yliopisto
 Organización Médica de Investigación
 Fundación para el estudio del Glaucoma
 Clinique Spécialisée en Ophtalmologie Mohammedia
 Eskişehir Osmangazi Üniversitesi
 Ufa Eye Research Institute
 Seoul National University Hospital
 Yeungnam University, College of Medicine
 Kyoto University
 Otsu Red Cross Hospital
 Instituto de Oftalmología Fundación Conde de Valenciana
 Universidad Nacional Autónoma de México
 Universität Heidelberg
 Beijing Tongren Hospital
 Narayana Nethralaya Eye Hospital
 Chichua Medical Center Mzera, LLC
 Medical Research Foundation, Chennai
 Vietnam National Institute of Ophthalmology
 King Khaled Eye Specialist Hospital
 University of Illinois Eye Center
 Hospital Universitario de Salamanca
 Institute for Biomedical Research of Salamanca (IBSAL)
 SBUMS Ophthalmic Research Center
 University of Tehran
 Ideta Eye Hospital
 Rigshospitalet
 University of Utah Health
 University of Electronic Science and Technology of China
 Xinjiang Medical University
 Sichuan Provincial People's Hospital
 Chinese Academy of Sciences
 Jinan University
 CHU Angers
 Tbilisi State Medical University
 Friedrich-Alexander-Universität Erlangen-Nürnberg
 Medizinische Universität Graz
 Universität Tübingen
 Aristotle University of Thessaloniki
 Narayana Nethralaya Foundation
 Santa Lucia Eye Hospital from Buenos Aires
 Vision Research Foundation India
 Shahid Beheshti University of Medical Sciences

Abstract

© 2017 Nature America, Inc., part of Springer Nature. All rights reserved. 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.

Keyword(s)

Biochemistry, Genetics and Molecular Biology

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/41856

Collections

Scopus 2016-2017