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Nat Genet. 2017 Jul;49(7):993-1004. doi: 10.1038/ng.3875. Epub 2017 May 29.

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

Aung T1,2,3, Ozaki M4,5, Lee MC1,6, Schlötzer-Schrehardt U7, Thorleifsson G8, Mizoguchi T9, Igo RP Jr10, Haripriya A11, Williams SE12, Astakhov YS13, Orr AC14,15, Burdon KP16,17, Nakano S18, Mori K19, Abu-Amero K20,21, Hauser M1,22,23, Li Z24, Prakadeeswari G25, Bailey JNC10, Cherecheanu AP26,27, Kang JH28, Nelson S29, Hayashi K30, Manabe SI30, Kazama S31, Zarnowski T32, Inoue K33, Irkec M34, Coca-Prados M35,36,37, Sugiyama K38, Järvelä I39, Schlottmann P40, Lerner SF41, Lamari H42, Nilgün Y43, Bikbov M44, Park KH45, Cha SC46, Yamashiro K47,48, Zenteno JC49,50, Jonas JB51,52, Kumar RS53, Perera SA1,2, Chan ASY1,2,6, Kobakhidze N54, George R55, Vijaya L55, Do T56, Edward DP57,58, de Juan Marcos L59,60, Pakravan M61, Moghimi S62, Ideta R63, Bach-Holm D64, Kappelgaard P64, Wirostko B65, Thomas S65, Gaston D15, Bedard K15, Greer WL15, Yang Z66,67, Chen X68, Huang L69,70, Sang J52, Jia H52, Jia L52,71, Qiao C52, Zhang H52, Liu X72, Zhao B52,71, Wang YX71, Xu L52, Leruez S73, Reynier P74, Chichua G54, Tabagari S75, Uebe S76, Zenkel M7, Berner D7, Mossböck G77, Weisschuh N78, Hoja U7, Welge-Luessen UC7, Mardin C7, Founti P79, Chatzikyriakidou A80, Pappas T79, Anastasopoulos E79, Lambropoulos A80, Ghosh A81, Shetty R53, Porporato N82, Saravanan V25, Venkatesh R83, Shivkumar C84, Kalpana N85, Sarangapani S86, Kanavi MR87, Beni AN61, Yazdani S61, Lashay A62, Naderifar H62, Khatibi N62, Fea A88, Lavia C88, Dallorto L88, Rolle T88, Frezzotti P89, Paoli D90, Salvi E91, Manunta P92, Mori Y93, Miyata K93, Higashide T38, Chihara E94, Ishiko S95, Yoshida A96, Yanagi M97, Kiuchi Y97, Ohashi T98, Sakurai T99, Sugimoto T5, Chuman H5, Aihara M100, Inatani M101, Miyake M47, Gotoh N102, Matsuda F102, Yoshimura N47,103, Ikeda Y19, Ueno M19, Sotozono C19, Jeoung JW45, Sagong M46, Park KH104, Ahn J105, Cruz-Aguilar M49, Ezzouhairi SM42, Rafei A106, Chong YF1, Ng XY1, Goh SR1, Chen Y1, Yong VHK1, Khan MI107, Olawoye OO108,109, Ashaye AO108,109, Ugbede I110, Onakoya A111,112, Kizor-Akaraiwe N113,114, Teekhasaenee C115, Suwan Y115, Supakontanasan W115, Okeke S113,114, Uche NJ114,116,117, Asimadu I113, Ayub H118, Akhtar F119, Kosior-Jarecka E32, Lukasik U32, Lischinsky I120, Castro V121, Grossmann RP122, Sunaric Megevand G123, Roy S123, Dervan E124, Silke E124, Rao A125, Sahay P125, Fornero P126, Cuello O126, Sivori D41, Zompa T127, Mills RA16, Souzeau E16, Mitchell P128, Wang JJ128, Hewitt AW17,129, Coote M129, Crowston JG129, Astakhov SY13, Akopov EL13, Emelyanov A13,130, Vysochinskaya V130, Kazakbaeva G44, Fayzrakhmanov R44, Al-Obeidan SA20, Owaidhah O57, Aljasim LA57, Chowbay B131,132,133, Foo JN24,134, Soh RQ24, Sim KS24, Xie Z24, Cheong AWO24, Mok SQ24, Soo HM24, Chen XY24, Peh SQ24, Heng KK24, Husain R2, Ho SL135, Hillmer AM24, Cheng CY1,2,3,6, Escudero-Domínguez FA59, González-Sarmiento R60,136, Martinon-Torres F137,138, Salas A139,140, Pathanapitoon K141, Hansapinyo L141, Wanichwecharugruang B142, Kitnarong N143, Sakuntabhai A144,145, Nguyn HX56, Nguyn GTT56, Nguyn TV56, Zenz W146, Binder A146, Klobassa DS146, Hibberd ML24,147, Davila S24, Herms S148,149,150, Nöthen MM148,151, Moebus S152, Rautenbach RM153, Ziskind A153, Carmichael TR12, Ramsay M154, Álvarez L35,36, García M35,36, González-Iglesias H35,36, Rodríguez-Calvo PP35,36, Fernández-Vega Cueto L#35,36, Oguz Ç155, Tamcelik N156, Atalay E1,156, Batu B156, Aktas D157, Kasım B34, Wilson MR158, Coleman AL159, Liu Y160, Challa P22, Herndon L22, Kuchtey RW161, Kuchtey J161, Curtin K65, Chaya CJ65, Crandall A65, Zangwill LM162, Wong TY1,2,3, Nakano M163, Kinoshita S19,164, den Hollander AI107,165, Vesti E166, Fingert JH167,168, Lee RK169, Sit AJ170, Shingleton BJ171, Wang N52,71, Cusi D172, Qamar R173,174, Kraft P175, Pericak-Vance MA176, Raychaudhuri S177,178,179,180,181, Heegaard S182,183, Kivelä T184, Reis A75, Kruse FE7, Weinreb RN162, Pasquale LR28,185, Haines JL10,186, Thorsteinsdottir U8,187, Jonasson F187,188, Allingham RR1,22, Milea D1,2,6, Ritch R189, Kubota T18, Tashiro K163, Vithana EN1,3, Micheal S165, Topouzis F79, Craig JE16, Dubina M13,130, Sundaresan P190, Stefansson K8,187, Wiggs JL185, Pasutto F76, Khor CC1,24,191.

Author information

1
Singapore Eye Research Institute, Singapore.
2
Singapore National Eye Center, Singapore.
3
Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
4
Ozaki Eye Hospital, Hyuga, Miyazaki, Japan.
5
Department of Ophthalmology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
6
Academic Clinical Program for Ophthalmology and Visual Sciences, Office of Clinical and Academic Faculty Affairs, Duke-NUS Graduate Medical School, Singapore.
7
Department of Ophthalmology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
8
deCODE Genetics, Reykjavik, Iceland.
9
Mizoguchi Eye Hospital, Sasebo, Japan.
10
Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
11
Aravind Eye Hospital, Madurai, India.
12
Division of Ophthalmology, University of the Witwatersrand, Johannesburg, South Africa.
13
Department of Ophthalmology, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia.
14
Department of Ophthalmology, Dalhousie University, Halifax, Nova Scotia, Canada.
15
Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
16
Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
17
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
18
Department of Ophthalmology, Oita University Faculty of Medicine, Oita, Japan.
19
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
20
Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
21
Department of Ophthalmology, College of Medicine, University of Florida, Jacksonville, Florida, USA.
22
Department of Ophthalmology, Duke University Eye Center, Durham, North Carolina, USA.
23
Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
24
Genome Institute of Singapore, Singapore.
25
Department of Genetics, Aravind Medical Research Foundation, Madurai, India.
26
'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania.
27
Department of Ophthalmology, University Emergency Hospital, Bucharest, Romania.
28
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
29
Department of Biostatistics, University of Washington, Seattle, Washington, USA.
30
Hayashi Eye Hospital, Fukuoka, Japan.
31
Shinjo Eye Clinic, Miyazaki, Japan.
32
Department of Diagnostics and Microsurgery of Glaucoma, Medical University, Lublin, Poland.
33
Inoue Eye Hospital, Tokyo, Japan.
34
Department of Ophthalmology, Hacettepe University, Faculty of Medicine, Ankara, Turkey.
35
Fernández-Vega University Institute and Foundation of Ophthalmological Research, University of Oviedo, Oviedo, Spain.
36
Fernández-Vega Ophthalmological Institute, Oviedo, Spain.
37
Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, Connecticut, USA.
38
Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
39
Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
40
Organización Médica de Investigación, Buenos Aires, Argentina.
41
Fundación para el Estudio del Glaucoma, Buenos Aires, Argentina.
42
Clinique Spécialisée en Ophtalmologie Mohammedia, Mohammedia, Morocco.
43
Department of Ophthalmology, Eskisehir Osmangazi University, Meselik, Eskisehir, Turkey.
44
Ufa Eye Research Institute, Ufa, Russia.
45
Department of Ophthalmology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
46
Department of Ophthalmology, Yeungnam University College of Medicine, Daegu, Republic of Korea.
47
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
48
Department of Ophthalmology, Otsu Red Cross Hospital, Otsu, Japan.
49
Genetics Department, Institute of Ophthalmology 'Conde de Valenciana', Mexico City, Mexico.
50
Biochemistry Department, Faculty of Medicine, UNAM, Mexico City, Mexico.
51
Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht Karls University of Heidelberg, Mannheim, Germany.
52
Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Science Key Laboratory, Beijing, China.
53
Narayana Nethralaya Eye Hospital, Bangalore, India.
54
Chichua Medical Center Mzera, LLC, Tbilisi, Georgia.
55
Jadhavbhai Nathamal Singhvi Department of Glaucoma, Medical Research Foundation, Chennai, India.
56
Vietnam National Institute of Ophthalmology, Hanoi, Vietnam.
57
King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
58
Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
59
Department of Ophthalmology, University Hospital of Salamanca, Salamanca, Spain.
60
Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
61
Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
62
Farabi Eye Hospital, Tehran University Eye Research Center, Tehran University of Medical Sciences, Tehran, Iran.
63
Ideta Eye Hospital, Kumamoto City, Japan.
64
Eye Clinic, Rigshospitalet-Glostrup, Glostrup, Denmark.
65
John A. Moran Eye Center, Department of Ophthalmology, University of Utah, Salt Lake City, Utah, USA.
66
Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
67
School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
68
Department of Ophthalmology, First Affiliated Hospital of Xinjiang Medical University, Urumchi, China.
69
Center for Human Molecular Biology and Genetics, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.
70
Sichuan Translational Research Hospital, Chinese Academy of Sciences, Chengdu, China.
71
Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
72
Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, Jinan University, Shenzhen, China.
73
Département d'Ophtalmologie, Centre Hospitalier Universitaire, Angers, France.
74
Département de Biochimie et Génétique, Centre Hospitalier Universitaire, Angers, France.
75
David Tvildiani Medical University, Tbilisi, Georgia.
76
Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
77
Department of Ophthalmology, Medical University Graz, Graz, Austria.
78
Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
79
Department of Ophthalmology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
80
Laboratory of General Biology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
81
GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore, India.
82
Santa Lucia Eye Hospital from Buenos Aires, Buenos Aires, Argentina.
83
Aravind Eye Hospital, Pondicherry, India.
84
Aravind Eye Hospital, Tirunelveli, India.
85
Aravind Eye Hospital, Coimbatore, India.
86
Vision Research Foundation, Chennai, India.
87
Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
88
Dipartimento di Scienze Chirurgiche, Università di Torino, Turin, Italy.
89
Ophthalmology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
90
Department of Ophthalmology, Monfalcone Hospital, Gorizia, Italy.
91
Department of Health Sciences, University of Milan, Milan, Italy.
92
Department of Nephrology, University Vita-Salute San Raffaele, Milan, Italy.
93
Miyata Eye Hospital, Miyazaki, Japan.
94
Sensho-kai Eye Institute, Kyoto, Japan.
95
Department of Medicine and Engineering Combined Research Institute, Asahikawa Medical University, Asahikawa, Japan.
96
Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.
97
Department of Ophthalmology and Visual Sciences, Hiroshima University, Hiroshima, Japan.
98
Ohashi Eye Center, Sapporo, Japan.
99
Tane Memorial Eye Hospital, Osaka, Japan.
100
Department of Ophthalmology, University of Tokyo, Tokyo, Japan.
101
Department of Ophthalmology, Faculty of Medical Science, University of Fukui, Fukui, Japan.
102
Center for Genomic Medicine, INSERM U852, Kyoto University Graduate School of Medicine, Kyoto, Japan.
103
Tazuke Kofukai Foundation, Medical Research Institute, Kitano Hospital, Osaka, Japan.
104
Department of Ophthalmology, Seoul National University Bundang Hospital, Gyeonggi, Republic of Korea.
105
Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea.
106
Laboratoires RAFEI, Mohammedia, Morocco.
107
Department of Human Genetics, Radboud University Medical Centre, Nijmegen, the Netherlands.
108
Department of Ophthalmology, College of Medicine, University of Ibadan, Ibadan, Nigeria.
109
Department of Ophthalmology, University College Hospital, Ibadan, Nigeria.
110
ECWA Eye Hospital, Kano, Nigeria.
111
Department of Ophthalmology, University of Lagos, Lagos, Nigeria.
112
Guinness Eye Centre, Lagos University Teaching Hospital, Lagos, Nigeria.
113
Department of Ophthalmology, ESUT Teaching Hospital Parklane, Enugu, Nigeria.
114
Eye Specialists Hospital, Enugu, Nigeria.
115
Department of Ophthalmology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
116
Department of Ophthalmology, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria.
117
Department of Ophthalmology, College of Medicine, University of Nigeria, Nsukka, Ituku Ozalla Campus, Enugu, Nigeria.
118
Department of Environmental Sciences, COMSATS Institute of Information Technology, Abbottabad, Pakistan.
119
Pakistan Institute of Ophthalmology, Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan.
120
Centro Oftalmologico Lischinsky, Tucumán, Argentina.
121
Universidad Peruana Cayetano Heredia, Hospital Nacional Arzobispo Loayza, Lima, Peru.
122
Instituto de Glaucoma y Catarata, Lima, Peru.
123
Clinical Research Centre Adolphe de Rothschild, Société Médicale de Beaulieu, Geneva, Switzerland.
124
Mater Misericordiae University Hospital, Dublin, Ireland.
125
Shri Mithu Tulsi, LV Prasad Eye Institute, Bhubaneswar, India.
126
Hospital Córdoba, Córdoba, Argentina.
127
Centro Oftalmologico Charles, Buenos Aires, Argentina.
128
Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
129
Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
130
St. Petersburg Academic University, St. Petersburg, Russia.
131
Clinical Pharmacology, SingHealth, Singapore.
132
Clinical Pharmacology Laboratory, National Cancer Centre, Singapore.
133
Office of Clinical Sciences, Duke-NUS Medical School, Singapore.
134
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
135
Department of Ophthalmology, Tan Tock Seng Hospital, Singapore.
136
Molecular Medicine Unit, Department of Medicine, University of Salamanca, Salamanca, Spain.
137
Translational Pediatrics and Infectious Diseases, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain.
138
GENVIP Research Group, Instituto de Investigación Sanitaria de Santiago, Santiago de Compostela, Spain.
139
Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
140
Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
141
Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
142
Department of Ophthalmology, Rajavithi Hospital, Bangkok, Thailand.
143
Department of Ophthalmology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
144
Institut Pasteur, Functional Genetics of Infectious Diseases Unit, Department of Genomes and Genetics, Paris, France.
145
Centre National de la Recherche Scientifique, Unité de Recherche Associée 3012, Paris, France.
146
Department of General Pediatrics, Medical University of Graz, Graz, Austria.
147
Faculty of Infectious and Tropical Disease, London School of Hygiene and Tropical Medicine, London, UK.
148
Department of Genomics, Life &Brain Center, University of Bonn, Bonn, Germany.
149
Department of Biomedicine, University of Basel, Basel, Switzerland.
150
Division of Medical Genetics, University Hospital Basel, Basel, Switzerland.
151
Institute of Human Genetics, University of Bonn, Bonn, Germany.
152
Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany.
153
Division of Ophthalmology, Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa.
154
Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
155
Department of Genetics, Eskisehir Osmangazi University, Meselik, Eskisehir, Turkey.
156
Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey.
157
DAMAGEN Genetic Diagnostic Center, Ankara, Turkey.
158
School of Medicine, Wayne State University, Detroit, Michigan, USA.
159
Center for Community Outreach and Policy, Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
160
Department of Cellular Biology and Anatomy, Center for Biotechnology and Genomic Medicine, James and Jean Culver Discovery Institute, Augusta University, Augusta, Georgia, USA.
161
Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
162
Hamilton Glaucoma Center, Department of Ophthalmology and Shiley Eye Institute, University of California, San Diego, San Diego, California, USA.
163
Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan.
164
Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
165
Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands.
166
Department of Ophthalmology, University of Turku and Turku University Hospital, Turku, Finland.
167
Institute for Vision Research, University of Iowa, Iowa City, Iowa, USA.
168
Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
169
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.
170
Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA.
171
Ophthalmic Consultants of Boston, Boston, Massachusetts, USA.
172
Institute of Biomedical Technologies, Italian National Research Centre (ITB-CNR), Segrate-Milano, Italy.
173
Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
174
Department of Biochemistry, Al-Nafees Medical College and Hospital, Isra University, Islamabad, Pakistan.
175
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
176
John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
177
Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
178
Partners Center for Personalized Genetic Medicine, Boston, Massachusetts, USA.
179
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
180
Institute of Inflammation and Repair, University of Manchester, Manchester, UK.
181
Rheumatology Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden.
182
Department of Ophthalmology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
183
Department of Pathology, Rigshospitalet, Eye Pathology Section, University of Copenhagen, Copenhagen, Denmark.
184
Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
185
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
186
Institute of Computational Biology, Case Western Reserve University, Cleveland, Ohio, USA.
187
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
188
Department of Ophthalmology, Landspitali University Hospital, Reykjavik, Iceland.
189
Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, New York, USA.
190
Dr. G.Venkataswamy Eye Research Institute, Aravind Medical Research Foundation, Aravind Eye Hospital, Madurai, India.
191
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
#
Contributed equally

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.

PMID:
28553957
DOI:
10.1038/ng.3875
[Indexed for MEDLINE]

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