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Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci
- Source :
- Aung , T , Ozaki , M , Lee , M C , Schlotzer-Schrehardt , U , Thorleifsson , G , Mizoguchi , T , Igo , R P J , Haripriya , A , Williams , S E , Astakhov , Y S , Orr , A C , Burdon , K P , Nakano , S , Mori , K , Abu-Amero , K , Hauser , M , Li , Z , Prakadeeswari , G , Bailey , J N C , Cherecheanu , A P , Kang , J H , Nelson , S , Hayashi , K , Manabe , S , Kazama , S , Zarnowski , T , Inoue , K , Irkec , M , Coca-Prados , M , Sugiyama , K , Jarvela , I , Schlottmann , P , Lerner , S F , Lamari , H , Nilgun , Y , Bikbov , M , Park , K H , Cha , S C , Yamashiro , K , Zenteno , J C , Jonas , J B , Kumar , R S , Perera , S A , Chan , A S Y , Kobakhidze , N , George , R , Vijaya , L , Do , T , Edward , D P , de Juan Marcos , L , Pakravan , M , Moghimi , S , Ideta , R , Bach-Holm , D , Kappelgaard , P , Wirostko , B , Thomas , S , Gaston , D , Bedard , K , Greer , W L , Yang , Z , Chen , X , Huang , L , Sang , J , Jia , H , Jia , L , Qiao , C , Zhang , H , Liu , X , Zhao , B , Wang , Y-X , Xu , L , Leruez , S , Reynier , P , Chichua , G , Tabagari , S , Uebe , S , Zenkel , M , Berner , D , Mossboeck , G , Weisschuh , N , Hoja , U , Welge-Luessen , U-C , Mardin , C , Founti , P , Chatzikyriakidou , A , Pappas , T , Anastasopoulos , E , Lambropoulos , A , Ghosh , A , Shetty , R , Porporato , N , Saravanan , V , Venkatesh , R , Shivkumar , C , Kalpana , N , Sarangapani , S , Kanavi , M R , Beni , A N , Yazdani , S , Lashay , A , Naderifar , H , Khatibi , N , Fea , A , Lavia , C , Dallorto , L , Rolle , T , Frezzotti , P , Paoli , D , Salvi , E , Manunta , P , Mori , Y , Miyata , K , Higashide , T , Chihara , E , Ishiko , S , Yoshida , A , Yanagi , M , Kiuchi , Y , Ohashi , T , Sakurai , T , Sugimoto , T , Chuman , H , Aihara , M , Inatani , M , Miyake , M , Gotoh , N , Matsuda , F , Yoshimura , N , Ikeda , Y , Ueno , M , Sotozono , C , Jeoung , J W , Sagong , M , Park , K H , Ahn , J , Cruz-Aguilar , M , Ezzouhairi , S M , Rafei , A , Chong , Y F , Ng , X Y , Goh , S R , Ch
- Publication Year :
- 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.
Details
- Database :
- OAIster
- Journal :
- Aung , T , Ozaki , M , Lee , M C , Schlotzer-Schrehardt , U , Thorleifsson , G , Mizoguchi , T , Igo , R P J , Haripriya , A , Williams , S E , Astakhov , Y S , Orr , A C , Burdon , K P , Nakano , S , Mori , K , Abu-Amero , K , Hauser , M , Li , Z , Prakadeeswari , G , Bailey , J N C , Cherecheanu , A P , Kang , J H , Nelson , S , Hayashi , K , Manabe , S , Kazama , S , Zarnowski , T , Inoue , K , Irkec , M , Coca-Prados , M , Sugiyama , K , Jarvela , I , Schlottmann , P , Lerner , S F , Lamari , H , Nilgun , Y , Bikbov , M , Park , K H , Cha , S C , Yamashiro , K , Zenteno , J C , Jonas , J B , Kumar , R S , Perera , S A , Chan , A S Y , Kobakhidze , N , George , R , Vijaya , L , Do , T , Edward , D P , de Juan Marcos , L , Pakravan , M , Moghimi , S , Ideta , R , Bach-Holm , D , Kappelgaard , P , Wirostko , B , Thomas , S , Gaston , D , Bedard , K , Greer , W L , Yang , Z , Chen , X , Huang , L , Sang , J , Jia , H , Jia , L , Qiao , C , Zhang , H , Liu , X , Zhao , B , Wang , Y-X , Xu , L , Leruez , S , Reynier , P , Chichua , G , Tabagari , S , Uebe , S , Zenkel , M , Berner , D , Mossboeck , G , Weisschuh , N , Hoja , U , Welge-Luessen , U-C , Mardin , C , Founti , P , Chatzikyriakidou , A , Pappas , T , Anastasopoulos , E , Lambropoulos , A , Ghosh , A , Shetty , R , Porporato , N , Saravanan , V , Venkatesh , R , Shivkumar , C , Kalpana , N , Sarangapani , S , Kanavi , M R , Beni , A N , Yazdani , S , Lashay , A , Naderifar , H , Khatibi , N , Fea , A , Lavia , C , Dallorto , L , Rolle , T , Frezzotti , P , Paoli , D , Salvi , E , Manunta , P , Mori , Y , Miyata , K , Higashide , T , Chihara , E , Ishiko , S , Yoshida , A , Yanagi , M , Kiuchi , Y , Ohashi , T , Sakurai , T , Sugimoto , T , Chuman , H , Aihara , M , Inatani , M , Miyake , M , Gotoh , N , Matsuda , F , Yoshimura , N , Ikeda , Y , Ueno , M , Sotozono , C , Jeoung , J W , Sagong , M , Park , K H , Ahn , J , Cruz-Aguilar , M , Ezzouhairi , S M , Rafei , A , Chong , Y F , Ng , X Y , Goh , S R , Ch
- Notes :
- English
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1322699407
- Document Type :
- Electronic Resource