Tin AungMineo OzakiMei Chin LeeUrsula Schlötzer-SchrehardtGudmar ThorleifssonTakanori MizoguchiRobert P. IgoAravind HaripriyaSusan E. WilliamsYury S. AstakhovAndrew C. OrrKathryn P. BurdonSatoko NakanoKazuhiko MoriKhaled Abu-AmeroMichael HauserZheng LiGopalakrishnan PrakadeeswariJessica N.Cooke BaileyAlina Popa CherecheanuJae H. KangSarah NelsonKen HayashiShin Ichi ManabeShigeyasu KazamaTomasz ZarnowskiKenji InoueMurat IrkecMiguel Coca-PradosKazuhisa SugiyamaIrma JärveläPatricio SchlottmannS. Fabian LernerHasnaa LamariYildirim NilgünMukharram BikbovKi Ho ParkSoon Cheol ChaKenji YamashiroJuan C. ZentenoJost B. JonasRajesh S. KumarShamira A. PereraAnita S.Y. ChanNino KobakhidzeRonnie GeorgeLingam VijayaTan DoDeepak P. EdwardLourdes De Juan MarcosMohammad PakravanSasan MoghimiRyuichi IdetaDaniella Bach-HolmPer KappelgaardBarbara WirostkoSamuel ThomasDaniel GastonKaren BedardWenda L. GreerZhenglin YangXueyi ChenLulin HuangJinghong SangHongyan JiaLiyun JiaChunyan QiaoHui ZhangXuyang LiuBowen ZhaoYa Xing WangLiang XuStéphanie LeruezPascal ReynierGeorge ChichuaSergo TabagariSingapore Eye Research InstituteSingapore National Eye CentreYong Loo Lin School of MedicineOzaki Eye HospitalUniversity of MiyazakiDuke-NUS Medical School SingaporeUniversitätsklinik Erlangen und Medizinische FakultätdeCODE geneticsMizoguchi Eye ClinicCase Western Reserve UniversityAravind Eye HospitalUniversity of WitwatersrandPavlov UniversityDalhousie UniversityFlinders UniversityUniversity of TasmaniaOita UniversityKyoto Prefectural University of MedicineKing Saud University Medical CollegeUniversity of FloridaDuke University Eye CenterDuke University Medical CenterA-Star, Genome Institute of SingaporeAravind Medical Research FoundationUniversitatea de Medicina si Farmacie Carol Davila din BucurestiUniversity Emergency HospitalBrigham and Women's HospitalUniversity of Washington, SeattleHayashi Eye HospitalShinjo Eye ClinicMedical University of LublinInoue Eye HospitalHacettepe ÜniversitesiUniversidad de OviedoFernández-Vega Ophthalmological InstituteYale University School of MedicineKanazawa University School of MedicineHelsingin YliopistoOrganización Médica de InvestigaciónFundación para el estudio del GlaucomaClinique Spécialisée en Ophtalmologie MohammediaEskişehir Osmangazi ÜniversitesiUfa Eye Research InstituteSeoul National University HospitalYeungnam University, College of MedicineKyoto UniversityOtsu Red Cross HospitalInstituto de Oftalmología Fundación Conde de ValencianaUniversidad Nacional Autónoma de MéxicoUniversität HeidelbergBeijing Tongren HospitalNarayana Nethralaya Eye HospitalChichua Medical Center Mzera, LLCMedical Research Foundation, ChennaiVietnam National Institute of OphthalmologyKing Khaled Eye Specialist HospitalUniversity of Illinois Eye CenterHospital Universitario de SalamancaInstitute for Biomedical Research of Salamanca (IBSAL)SBUMS Ophthalmic Research CenterUniversity of TehranIdeta Eye HospitalRigshospitaletUniversity of Utah HealthUniversity of Electronic Science and Technology of ChinaXinjiang Medical UniversitySichuan Provincial People's HospitalChinese Academy of SciencesJinan UniversityCHU AngersTbilisi State Medical UniversityFriedrich-Alexander-Universität Erlangen-NürnbergMedizinische Universität GrazUniversität TübingenAristotle University of ThessalonikiNarayana Nethralaya FoundationSanta Lucia Eye Hospital from Buenos AiresVision Research Foundation IndiaShahid Beheshti University of Medical Sciences2018-12-212019-03-142018-12-212019-03-142017-07-01Nature Genetics. Vol.49, No.7 (2017), 993-100415461718106140362-s2.0-85021706287https://repository.li.mahidol.ac.th/handle/20.500.14594/41856© 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1038/ng.3875