Journal article
Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci
Nature Genetics, Vol.49(7), pp.993-1004
05/29/2017
DOI: 10.1038/ng.3875
PMID: 28553957
Abstract
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.
Details
- Title: Subtitle
- Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci
- Creators
- Sasan MoghimiJost Jonas - Universität Heidelberg [Heidelberg]Irma Järvelä - Department of Medical and Clinical Genetics [Helsinki]Jae Kang - Harvard Medical School [Boston]Ryuichi IdetaRajesh Kumar - Birla Institute of Scientific ResearchPatricio Schlottmann - Organizacion Medica de InvestigacionSarah Nelson - University of Washington [Seattle]Daniella Bach-HolmShamira PereraS. Fabian Lerner - Fundacion para el Estudio del Glaucoma [Buenos Aires]Ken Hayashi - Hayashi Eye Hospital [Fukuoka]Per KappelgaardAnita ChaHasnaa Lamari - Chercheur indépendantShin-ichi Manabe - Hayashi Eye Hospital [Fukuoka]Barbara WirostkoNino KobakhidzeYildirim Nilgün - Eskisehir Osmangazi UniversityShigeyasu Kazama - Shinjo Eye Clinic [Nagoya]Samuel ThomasRonnie GeorgeMukharram Bikbov - Ufa Eye Research Institute [Bashkortostan]Tomasz Zarnowski - Medical University of LublinDaniel Gaston - Faculty of Computer ScienceTan DoKi Ho Park - Seoul National University HospitalKen Inoue - Inoue Eye Hospital [Tokyo]Karen Bedard - Department of Pathology and ImmunologyDeepak EdwardSoon Cheol Cha - Yeungnam University [South Korea]Murat Irkec - Hacettepe University = Hacettepe ÜniversitesiWenda GreerJuan de Juan MarcosKen Yamashiro - Kyoto University [Kyoto]Miguel Coca-Prados - Universidad de Oviedo [Oviedo]Kazuhisa Sugiyama - Kanazawa UniversityJuan Zenteno - Universidad Nacional Autónoma de MéxicoMohammad PakravanZheng YangTin Aung - Singapore Eye Research Institute [Singapore]Lulin HuangMineo Ozaki - Ozaki Eye Hospital [Miyazaki]Jinghong SangMei Chin Lee - Singapore Eye Research Institute [Singapore]Hongyan JiaUrsula Schlötzer-Schrehardt - Friedrich-Alexander Universität Erlangen-NürnbergLiyun LiGudmar Thorleifsson - deCODE genetics [Reykjavik]Chunyan QiaoTakanori Mizoguchi - Mizoguchi Eye Hospital [Sasebo]Hui Zhang - Beijing Jishuitan HospitalRobert Igo - Case Western Reserve University [Cleveland]Xuyang LiAravind Haripriya - Aravind Eye Hospital [Madurai, India]Bowen ZhaoSusan Williams - University of the Witwatersrand [Johannesburg]Yury Astakhov - Pavlov First Saint Petersburg State Medical University [St. Petersburg]Liang LiAndrew Orr - Dalhousie University [Halifax]Stéphanie Leruez - Centre Hospitalier Universitaire d'AngersKathryn Burdon - Flinders University [Adelaide, Australia]Pascal Reynier - Centre Hospitalier Universitaire d'AngersSatoko Nakano - Kyoto Prefectural University of Medicine [Kyoto, Japon]George ChichuaKazuhiko Mori - Kyoto Prefectural University of Medicine [Kyoto, Japon]Sergo TabagariKhaled Abu-Amero - King Saud University [Riyadh]Steffen Uebe - Institute of Human Genetics [Erlangen, Allemagne]Michael Hauser - Singapore Eye Research Institute [Singapore]Matthias Zenkel - Institute of Human Genetics [Erlangen, Allemagne]Zheng Li - Genome Institute of SingaporeDaniel BernerGopalakrishnan Prakadeeswari - Aravind Medical Research FoundationGeorg MossböckJessica Bailey - Case Western Reserve University [Cleveland]Nicole Weisschuh - Institute of Human Genetics [Erlangen, Allemagne]Alina Popa Cherecheanu - Université de Médecine Carol DavilaUrsula HojaUlrich-Christoph Welge-LuessenChristian MardinPanayiota Founti - Department of Ophthalmology, School of Medicine [Thessaloniki, Grèce]Anthi ChaTheofanis PappasEleftherios Anastasopoulos - Aristotle University of ThessalonikiAlexandros LambropoulosArkasubhra GhoshRohit ShettyNatalia PorporatoVijayan VijayaRengaraj VenkateshChandrashekaran ChaNarendran KalpanaSripriya SarangapaniMozhgan KanaviAfsaneh Naderi BeniLingam LiShahin YazdaniYa-Xing WangXueyi Chen
- Contributors
- Anavaj Sakuntabhai (Editor)John H Fingert (Contributor) - University of Iowa, Ophthalmology and Visual Sciences
- Resource Type
- Journal article
- Publication Details
- Nature Genetics, Vol.49(7), pp.993-1004
- DOI
- 10.1038/ng.3875
- PMID
- 28553957
- NLM abbreviation
- Nat Genet
- ISSN
- 1061-4036
- eISSN
- 1546-1718
- Publisher
- Nature Publishing Group
- Language
- English
- Date published
- 05/29/2017
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9983979955002771
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