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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

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.
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