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Genetic Association Study of Exfoliation Syndrome Identifies a Protective Rare Variant at Loxl1 and Five New Susceptibility Loci Publisher Pubmed



Aung T1, 2, 3 ; Ozaki M4, 5 ; Lee MC1, 6 ; Schlotzerschrehardt U7 ; Thorleifsson G8 ; Mizoguchi T9 ; Igo RP10 ; Haripriya A11 ; Williams SE12 ; Astakhov YS13 ; Orr AC14, 15 ; Burdon KP16, 17 ; Nakano S18 ; Mori K19 Show All Authors
Authors
  1. Aung T1, 2, 3
  2. Ozaki M4, 5
  3. Lee MC1, 6
  4. Schlotzerschrehardt U7
  5. Thorleifsson G8
  6. Mizoguchi T9
  7. Igo RP10
  8. Haripriya A11
  9. Williams SE12
  10. Astakhov YS13
  11. Orr AC14, 15
  12. Burdon KP16, 17
  13. Nakano S18
  14. Mori K19
  15. Abuamero K20, 21
  16. Hauser M1, 22, 23
  17. Li Z24
  18. Prakadeeswari G25
  19. Bailey JNC10
  20. Cherecheanu AP26, 27
  21. Kang JH28
  22. Nelson S29
  23. Hayashi K30
  24. Manabe SI30
  25. Kazama S31
  26. Zarnowski T32
  27. Inoue K33
  28. Irkec M34
  29. Cocaprados M35, 36, 37
  30. Sugiyama K38
  31. Jarvela I39
  32. Schlottmann P40
  33. Lerner SF41
  34. Lamari H42
  35. Nilgun Y43
  36. Bikbov M44
  37. Park KH45
  38. Cha SC46
  39. Yamashiro K47, 48
  40. Zenteno JC49, 50
  41. Jonas JB51, 52
  42. Kumar RS53
  43. Perera SA1, 2
  44. Chan ASY1, 2, 6
  45. Kobakhidze N54
  46. George R55
  47. Vijaya L55
  48. Do T56
  49. Edward DP57, 58
  50. De Juan Marcos L59, 60
  51. Pakravan M61
  52. Moghimi S62
  53. Ideta R63
  54. Bachholm D64
  55. Kappelgaard P64
  56. Wirostko B65
  57. Thomas S65
  58. Gaston D15
  59. Bedard K15
  60. Greer WL15
  61. Yang Z66, 67
  62. Chen X68
  63. Huang L69, 70
  64. Sang J52
  65. Jia H52
  66. Jia L52, 71
  67. Qiao C52
  68. Zhang H52
  69. Liu X72
  70. Zhao B52, 71
  71. Wang YX71
  72. Xu L52
  73. Leruez S73
  74. Reynier P74
  75. Chichua G54
  76. Tabagari S75
  77. Uebe S76
  78. Zenkel M7
  79. Berner D7
  80. Mossbock G77
  81. Weisschuh N78
  82. Hoja U7
  83. Welgeluessen UC7
  84. Mardin C7
  85. Founti P79
  86. Chatzikyriakidou A80
  87. Pappas T79
  88. Anastasopoulos E79
  89. Lambropoulos A80
  90. Ghosh A81
  91. Shetty R53
  92. Porporato N82
  93. Saravanan V25
  94. Venkatesh R83
  95. Shivkumar C84
  96. Kalpana N85
  97. Sarangapani S86
  98. Kanavi MR87
  99. Beni AN61
  100. Yazdani S61
  101. Lashay A62
  102. Naderifar H62
  103. Khatibi N62
  104. Fea A88
  105. Lavia C88
  106. Dallorto L88
  107. Rolle T88
  108. Frezzotti P89
  109. Paoli D90
  110. Salvi E91
  111. Manunta P92
  112. Mori Y93
  113. Miyata K93
  114. Higashide T38
  115. Chihara E94
  116. Ishiko S95
  117. Yoshida A96
  118. Yanagi M97
  119. Kiuchi Y97
  120. Ohashi T98
  121. Sakurai T99
  122. Sugimoto T5
  123. Chuman H5
  124. Aihara M100
  125. Inatani M101
  126. Miyake M47
  127. Gotoh N102
  128. Matsuda F102
  129. Yoshimura N47, 103
  130. Ikeda Y19
  131. Ueno M19
  132. Sotozono C19
  133. Jeoung JW45
  134. Sagong M46
  135. Park KH45
  136. Ahn J105
  137. Cruzaguilar M49
  138. Ezzouhairi SM42
  139. Rafei A106
  140. Chong YF1
  141. Ng XY1
  142. Goh SR1
  143. Chen Y1
  144. Yong VHK1
  145. Khan MI107
  146. Olawoye OO108, 109
  147. Ashaye AO108, 109
  148. Ugbede I110
  149. Onakoya A111, 112
  150. Kizorakaraiwe N113, 114
  151. Teekhasaenee C115
  152. Suwan Y115
  153. Supakontanasan W115
  154. Okeke S113, 114
  155. Uche NJ114, 116, 117
  156. Asimadu I113
  157. Ayub H118
  158. Akhtar F119
  159. Kosiorjarecka E32
  160. Lukasik U32
  161. Lischinsky I120
  162. Castro V121
  163. Grossmann RP122
  164. Megevand GS123
  165. Roy S123
  166. Dervan E124
  167. Silke E124
  168. Rao A125
  169. Sahay P125
  170. Fornero P126
  171. Cuello O126
  172. Sivori D41
  173. Zompa T127
  174. Mills RA16
  175. Souzeau E16
  176. Mitchell P128
  177. Wang JJ128
  178. Hewitt AW17, 129
  179. Coote M129
  180. Crowston JG129
  181. Astakhov SY13
  182. Akopov EL13
  183. Emelyanov A13, 130
  184. Vysochinskaya V130
  185. Kazakbaeva G44
  186. Fayzrakhmanov R44
  187. Alobeidan SA20
  188. Owaidhah O57
  189. Aljasim LA57
  190. Chowbay B131, 132, 133
  191. Foo JN24, 134
  192. Soh RQ24
  193. Sim KS24
  194. Xie Z24
  195. Cheong AWO24
  196. Mok SQ24
  197. Soo HM24
  198. Chen XY24
  199. Peh SQ24
  200. Heng KK24
  201. Husain R2
  202. Ho SL135
  203. Hillmer AM24
  204. Cheng CY1, 2, 3, 6
  205. Escuderodominguez FA59
  206. Gonzalezsarmiento R60, 136
  207. Martinontorres F137, 138
  208. Salas A139
  209. Pathanapitoon K141
  210. Hansapinyo L141
  211. Wanichwecharugruang B142
  212. Kitnarong N143
  213. Sakuntabhai A144, 145
  214. Nguyn HX56
  215. Nguyn GTT56
  216. Nguyn TV56
  217. Zenz W146
  218. Binder A146
  219. Klobassa DS146
  220. Hibberd ML24, 147
  221. Davila S24
  222. Herms S148, 149, 150
  223. Nothen MM148, 151
  224. Moebus S152
  225. Rautenbach RM153
  226. Ziskind A153
  227. Carmichael TR12
  228. Ramsay M154
  229. Alvarez L35, 36
  230. Garcia M35, 36
  231. Gonzaleziglesias H35, 36
  232. Rodriguezcalvo PP35, 36
  233. Cueto LFV35, 36
  234. Oguz C155
  235. Tamcelik N156
  236. Atalay E1, 156
  237. Batu B156
  238. Aktas D157
  239. Kaslm B34
  240. Wilson MR158
  241. Coleman AL159
  242. Liu Y160
  243. Challa P22
  244. Herndon L22
  245. Kuchtey RW161
  246. Kuchtey J161
  247. Curtin K65
  248. Chaya CJ65
  249. Crandall A65
  250. Zangwill LM162
  251. Wong TY1, 2, 3
  252. Nakano M163
  253. Kinoshita S19, 164
  254. Den Hollander AI107, 165
  255. Vesti E166
  256. Fingert JH167, 168
  257. Lee RK169
  258. Sit AJ170
  259. Shingleton BJ171
  260. Wang N52, 71
  261. Cusi D172
  262. Qamar R173, 174
  263. Kraft P175
  264. Pericakvance MA176
  265. Raychaudhuri S177, 181
  266. Heegaard S182, 183
  267. Kivela T184
  268. Reis A75
  269. Kruse FE7
  270. Weinreb RN162
  271. Pasquale LR28, 185
  272. Haines JL10, 186
  273. Thorsteinsdottir U8, 187
  274. Jonasson F187, 188
  275. Allingham RR1, 22
  276. Milea D1, 2, 6
  277. Ritch R180
  278. Kubota T18
  279. Tashiro K163
  280. Vithana EN1, 3
  281. Micheal S165
  282. Topouzis F79
  283. Craig JE16
  284. Dubina M13, 130
  285. Sundaresan P179
  286. Stefansson K8, 187
  287. Wiggs JL185
  288. Pasutto F76
  289. Khor CC1, 24, 178
Show Affiliations
Authors Affiliations
  1. 1. Singapore Eye Research Institute, Singapore, Singapore
  2. 2. Singapore National Eye Center, Singapore
  3. 3. Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  4. 4. Ozaki Eye Hospital, Hyuga, Miyazaki, Japan
  5. 5. Department of Ophthalmology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
  6. 6. Academic Clinical Program for Ophthalmology and Visual Sciences, Office of Clinical and Academic Faculty Affairs, Duke-NUS Graduate Medical School, Singapore, Singapore
  7. 7. Department of Ophthalmology, Universitatsklinikum Erlangen, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany
  8. 8. DeCODE Genetics, Reykjavik, Iceland
  9. 9. Mizoguchi Eye Hospital, Sasebo, Japan
  10. 10. Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, United States
  11. 11. Aravind Eye Hospital, Madurai, India
  12. 12. Division of Ophthalmology, University of the Witwatersrand, Johannesburg, South Africa
  13. 13. Department of Ophthalmology, Pavlov First Saint Petersburg State Medical University, St.-Petersburg, Russian Federation
  14. 14. Department of Ophthalmology, Dalhousie University, Halifax, NS, Canada
  15. 15. Department of Pathology, Dalhousie University, Halifax, NS, Canada
  16. 16. Department of Ophthalmology, Flinders University, Adelaide, SA, Australia
  17. 17. Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
  18. 18. Department of Ophthalmology, Oita University, Faculty of Medicine, Oita, Japan
  19. 19. Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
  20. 20. Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  21. 21. Department of Ophthalmology, College of Medicine, University of Florida, Jacksonville, FL, United States
  22. 22. Department of Ophthalmology, Duke University Eye Center, Durham, NC, United States
  23. 23. Department of Medicine, Duke University Medical Center, Durham, NC, United States
  24. 24. Genome Institute of Singapore, Singapore
  25. 25. Department of Genetics, Aravind Medical Research Foundation, Madurai, India
  26. 26. Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
  27. 27. Department of Ophthalmology, University Emergency Hospital, Bucharest, Romania
  28. 28. Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
  29. 29. Department of Biostatistics, University of Washington, Seattle, WA, United States
  30. 30. Hayashi Eye Hospital, Fukuoka, Japan
  31. 31. Shinjo Eye Clinic, Miyazaki, Japan
  32. 32. Department of Diagnostics and Microsurgery of Glaucoma, Medical University, Lublin, Poland
  33. 33. Inoue Eye Hospital, Tokyo, Japan
  34. 34. Department of Ophthalmology, Hacettepe University, Faculty of Medicine, Ankara, Turkey
  35. 35. Fernandez-Vega University Institute, Foundation of Ophthalmological Research, University of Oviedo, Oviedo, Spain
  36. 36. Fernandez-Vega Ophthalmological Institute, Oviedo, Spain
  37. 37. Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT, United States
  38. 38. Department of Ophthalmology, Kanazawa University, Graduate School of Medical Science, Kanazawa, Japan
  39. 39. Department of Medical Genetics, University of Helsinki, Helsinki, Finland
  40. 40. Organizacion Medica de Investigacion, Buenos Aires, Argentina
  41. 41. Fundacion para El Estudio Del Glaucoma, Buenos Aires, Argentina
  42. 42. Clinique Specialisee en Ophtalmologie Mohammedia, Mohammedia, Morocco
  43. 43. Department of Ophthalmology, Eskisehir Osmangazi University, Meselik, Eskisehir, Turkey
  44. 44. Ufa Eye Research Institute, Ufa, Russian Federation
  45. 45. Department of Ophthalmology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
  46. 46. Department of Ophthalmology, Yeungnam University College of Medicine, Daegu, South Korea
  47. 47. Department of Ophthalmology and Visual Sciences, Kyoto University, Graduate School of Medicine, Kyoto, Japan
  48. 48. Department of Ophthalmology, Otsu Red Cross Hospital, Otsu, Japan
  49. 49. Genetics Department, Institute of Ophthalmology Conde de Valenciana, Mexico City, Mexico
  50. 50. Biochemistry Department, Faculty of Medicine, UNAM, Mexico City, Mexico
  51. 51. Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht Karls University of Heidelberg, Mannheim, Germany
  52. 52. Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Science Key Laboratory, Beijing, China
  53. 53. Narayana Nethralaya Eye Hospital, Bangalore, India
  54. 54. Chichua Medical Center Mzera, LLC, Tbilisi, Georgia
  55. 55. Jadhavbhai Nathamal Singhvi Department of Glaucoma, Medical Research Foundation, Chennai, India
  56. 56. Vietnam National Institute of Ophthalmology, Hanoi, Viet Nam
  57. 57. King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia
  58. 58. Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States
  59. 59. Department of Ophthalmology, University Hospital of Salamanca, Salamanca, Spain
  60. 60. Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
  61. 61. Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  62. 62. Farabi Eye Hospital, Tehran University Eye Research Center, Tehran University of Medical Sciences, Tehran, Iran
  63. 63. Ideta Eye Hospital, Kumamoto City, Japan
  64. 64. Eye Clinic, Rigshospitalet-Glostrup, Glostrup, Denmark
  65. 65. John A. Moran Eye Center, Department of Ophthalmology, University of Utah, Salt Lake City, UT, United States
  66. 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. 67. School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
  68. 68. Department of Ophthalmology, First Affiliated Hospital of Xinjiang Medical University, Urumchi, China
  69. 69. Center for Human Molecular Biology and Genetics, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, Chengdu, China
  70. 70. Sichuan Translational Research Hospital, Chinese Academy of Sciences, Chengdu, China
  71. 71. Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
  72. 72. Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, Jinan University, Shenzhen, China
  73. 73. Departement d'Ophtalmologie, Centre Hospitalier Universitaire, Angers, France
  74. 74. Departement de Biochimie et Genetique, Centre Hospitalier Universitaire, Angers, France
  75. 75. David Tvildiani Medical University, Tbilisi, Georgia
  76. 76. Institute of Human Genetics, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany
  77. 77. Department of Ophthalmology, Medical University Graz, Graz, Austria
  78. 78. Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tubingen, Tubingen, Germany
  79. 79. Department of Ophthalmology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
  80. 80. Laboratory of General Biology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
  81. 81. GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore, India
  82. 82. Santa Lucia Eye Hospital from Buenos Aires, Buenos Aires, Argentina
  83. 83. Aravind Eye Hospital, Pondicherry, India
  84. 84. Aravind Eye Hospital, Tirunelveli, India
  85. 85. Aravind Eye Hospital, Coimbatore, India
  86. 86. Vision Research Foundation, Chennai, India
  87. 87. Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  88. 88. Dipartimento di Scienze Chirurgiche, Universita di Torino, Turin, Italy
  89. 89. Ophthalmology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
  90. 90. Department of Ophthalmology, Monfalcone Hospital, Gorizia, Italy
  91. 91. Department of Health Sciences, University of Milan, Milan, Italy
  92. 92. Department of Nephrology, University Vita-Salute San Raffaele, Milan, Italy
  93. 93. Miyata Eye Hospital, Miyazaki, Japan
  94. 94. Sensho-kai Eye Institute, Kyoto, Japan
  95. 95. Department of Medicine, Engineering Combined Research Institute, Asahikawa Medical University, Asahikawa, Japan
  96. 96. Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan
  97. 97. Department of Ophthalmology and Visual Sciences, Hiroshima University, Hiroshima, Japan
  98. 98. Ohashi Eye Center, Sapporo, Japan
  99. 99. Tane Memorial Eye Hospital, Osaka, Japan
  100. 100. Department of Ophthalmology, University of Tokyo, Tokyo, Japan
  101. 101. Department of Ophthalmology, Faculty of Medical Science, University of Fukui, Fukui, Japan
  102. 102. Center for Genomic Medicine, INSERM U852, Kyoto University Graduate School of Medicine, Kyoto, Japan
  103. 103. Tazuke Kofukai Foundation, Medical Research Institute, Kitano Hospital, Osaka, Japan
  104. 104. Department of Ophthalmology, Seoul National University Bundang Hospital, Gyeonggi, South Korea
  105. 105. Department of Ophthalmology, Seoul Metropolitan Government Seoul National University, Boramae Medical Center, Seoul, South Korea
  106. 106. Laboratoires RAFEI, Mohammedia, Morocco
  107. 107. Department of Human Genetics, Radboud University Medical Centre, Nijmegen, Netherlands
  108. 108. Department of Ophthalmology, College of Medicine, University of Ibadan, Ibadan, Nigeria
  109. 109. Department of Ophthalmology, University College Hospital, Ibadan, Nigeria
  110. 110. ECWA Eye Hospital, Kano, Nigeria
  111. 111. Department of Ophthalmology, University of Lagos, Lagos, Nigeria
  112. 112. Guinness Eye Centre, Lagos University Teaching Hospital, Lagos, Nigeria
  113. 113. Department of Ophthalmology, ESUT Teaching Hospital Parklane, Enugu, Nigeria
  114. 114. Eye Specialists Hospital, Enugu, Nigeria
  115. 115. Department of Ophthalmology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  116. 116. Department of Ophthalmology, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria
  117. 117. Department of Ophthalmology, College of Medicine, University of Nigeria, Ituku Ozalla Campus, Nsukka, Enugu, Nigeria
  118. 118. Department of Environmental Sciences, COMSATS Institute of Information Technology, Abbottabad, Pakistan
  119. 119. Pakistan Institute of Ophthalmology, Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan
  120. 120. Centro Oftalmologico Lischinsky, Tucuman, Argentina
  121. 121. Universidad Peruana Cayetano Heredia, Hospital Nacional Arzobispo Loayza, Lima, Peru
  122. 122. Instituto de Glaucoma y Catarata, Lima, Peru
  123. 123. Clinical Research Centre Adolphe de Rothschild, Societe Medicale de Beaulieu, Geneva, Switzerland
  124. 124. Mater Misericordiae University Hospital, Dublin, Ireland
  125. 125. Shri Mithu Tulsi, LV Prasad Eye Institute, Bhubaneswar, India
  126. 126. Hospital Cordoba, Cordoba, Argentina
  127. 127. Centro Oftalmologico Charles, Buenos Aires, Argentina
  128. 128. Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, Australia
  129. 129. Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, VIC, Australia
  130. 130. St. Petersburg Academic University, St.-Petersburg, Russian Federation
  131. 131. Clinical Pharmacology, SingHealth, Singapore, Singapore
  132. 132. Clinical Pharmacology Laboratory, National Cancer Centre, Singapore, Singapore
  133. 133. Office of Clinical Sciences, Duke-NUS Medical School, Singapore, Singapore
  134. 134. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
  135. 135. Department of Ophthalmology, Tan Tock Seng Hospital, Singapore, Singapore
  136. 136. Molecular Medicine Unit, Department of Medicine, University of Salamanca, Salamanca, Spain
  137. 137. Translational Pediatrics and Infectious Diseases, Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain
  138. 138. GENVIP Research Group, Instituto de Investigacion Sanitaria de Santiago, Santiago de Compostela, Spain
  139. 139. Unidade de Xenetica, Departamento de Anatomia Patoloxica e Ciencias Forenses, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
  140. 140. Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
  141. 141. Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
  142. 142. Department of Ophthalmology, Rajavithi Hospital, Bangkok, Thailand
  143. 143. Department of Ophthalmology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
  144. 144. Institut Pasteur, Functional Genetics of Infectious Diseases Unit, Department of Genomes and Genetics, Paris, France
  145. 145. Centre National de la Recherche Scientifique, Unite de Recherche Associee 3012, Paris, France
  146. 146. Department of General Pediatrics, Medical University of Graz, Graz, Austria
  147. 147. Faculty of Infectious and Tropical Disease, London School of Hygiene and Tropical Medicine, London, United Kingdom
  148. 148. Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany
  149. 149. Department of Biomedicine, University of Basel, Basel, Switzerland
  150. 150. Division of Medical Genetics, University Hospital Basel, Basel, Switzerland
  151. 151. Institute of Human Genetics, University of Bonn, Bonn, Germany
  152. 152. Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany
  153. 153. Division of Ophthalmology, Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa
  154. 154. Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
  155. 155. Department of Genetics, Eskisehir Osmangazi University, Meselik, Eskisehir, Turkey
  156. 156. Istanbul University, Cerrahpasa Faculty of Medicine, Istanbul, Turkey
  157. 157. DAMAGEN Genetic Diagnostic Center, Ankara, Turkey
  158. 158. School of Medicine, Wayne State University, Detroit, MI, United States
  159. 159. Center for Community Outreach and Policy, Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
  160. 160. Department of Cellular Biology and Anatomy, Center for Biotechnology and Genomic Medicine, James and Jean Culver Discovery Institute, Augusta University, Augusta, GA, United States
  161. 161. Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, United States
  162. 162. Hamilton Glaucoma Center, Department of Ophthalmology, Shiley Eye Institute, University of California, San Diego, San Diego, CA, United States
  163. 163. Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan
  164. 164. Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
  165. 165. Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, Netherlands
  166. 166. Department of Ophthalmology, University of Turku, Turku University Hospital, Turku, Finland
  167. 167. Institute for Vision Research, University of Iowa, Iowa City, IA, United States
  168. 168. Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, United States
  169. 169. Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, United States
  170. 170. Department of Ophthalmology, Mayo Clinic, Rochester, MN, United States
  171. 171. Ophthalmic Consultants of Boston, Boston, MA, United States
  172. 172. Institute of Biomedical Technologies, Italian National Research Centre (ITB-CNR), Segrate-Milano, Italy
  173. 173. Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan
  174. 174. Department of Biochemistry, Al-Nafees Medical College and Hospital, Isra University, Islamabad, Pakistan
  175. 175. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
  176. 176. John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
  177. 177. Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
  178. 178. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  179. 179. Dr. G.Venkataswamy Eye Research Institute, Aravind Medical Research Foundation, Aravind Eye Hospital, Madurai, India
  180. 180. Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, NY, United States
  181. 181. Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden
  182. 182. Department of Ophthalmology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  183. 183. Department of Pathology, Rigshospitalet, Eye Pathology Section, University of Copenhagen, Copenhagen, Denmark
  184. 184. Department of Ophthalmology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland
  185. 185. Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, United States
  186. 186. Institute of Computational Biology, Case Western Reserve University, Cleveland, OH, United States
  187. 187. Faculty of Medicine, University of Iceland, Reykjavik, Iceland
  188. 188. Department of Ophthalmology, Landspitali University Hospital, Reykjavik, Iceland

Source: Nature Genetics Published:2017


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