| Title: |
Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci |
| Authors: |
Aung, Tin; Ozaki, Mineo; Lee, Mei Chin; Schlotzer-Schrehardt, Ursula; Thorleifsson, Gudmar; Mizoguchi, Takanori; Igo, Robert P., Jr.; Haripriya, Aravind; Williams, Susan E.; Astakhov, Yury S.; Orr, Andrew C.; Burdon, Kathryn P.; Nakano, Satoko; Mori, Kazuhiko; Abu-Amero, Khaled; Hauser, Michael; Li, Zheng; Prakadeeswari, Gopalakrishnan; Bailey, Jessica N. Cooke; Cherecheanu, Alina Popa; Kang, Jae H.; Nelson, Sarah; Hayashi, Ken; Manabe, Shin-ichi; Kazama, Shigeyasu; Zarnowski, Tomasz; Inoue, Kenji; Irkec, Murat; Coca-Prados, Miguel; Sugiyama, Kazuhisa; Jarvela, Irma; Schlottmann, Patricio; Lerner, S. Fabian; Lamari, Hasnaa; Nilgun, Yildirim; Bikbov, Mukharram; Park, Ki Ho; Cha, Soon Cheol; Yamashiro, Kenji; Zenteno, Juan C.; Jonas, Jost B.; Kumar, Rajesh S.; Perera, Shamira A.; Chan, Anita S. Y.; Kobakhidze, Nino; George, Ronnie; Vijaya, Lingam; Do, Tan; Edward, Deepak P.; de Juan Marcos, Lourdes; Pakravan, Mohammad; Moghimi, Sasan; Ideta, Ryuichi; Bach-Holm, Daniella; Kappelgaard, Per; Wirostko, Barbara; Thomas, Samuel; Gaston, Daniel; Bedard, Karen; Greer, Wenda L.; Yang, Zhenglin; Chen, Xueyi; Huang, Lulin; Sang, Jinghong; Jia, Hongyan; Jia, Liyun; Qiao, Chunyan; Zhang, Hui; Liu, Xuyang; Zhao, Bowen; Wang, Ya-Xing; Xu, Liang; Leruez, Stephanie; Reynier, Pascal; Chichua, George; Tabagari, Sergo; Uebe, Steffen; Zenkel, Matthias; Berner, Daniel; Mossboeck, Georg; Weisschuh, Nicole; Hoja, Ursula; Welge-Luessen, Ulrich-Christoph; Mardin, Christian; Founti, Panayiota; Chatzikyriakidou, Anthi; Pappas, Theofanis; Anastasopoulos, Eleftherios; Lambropoulos, Alexandros; Ghosh, Arkasubhra; Shetty, Rohit; Porporato, Natalia; Saravanan, Vijayan; Venkatesh, Rengaraj; Shivkumar, Chandrashekaran; Kalpana, Narendran; Sarangapani, Sripriya; Kanavi, Mozhgan R.; Beni, Afsaneh Naderi; Yazdani, Shahin; Lashay, Alireza; Naderifar, Homa; Khatibi, Nassim; Fea, Antonio; Lavia, Carlo; Dallorto, Laura; Rolle, Teresa; Frezzotti, Paolo; Paoli, Daniela; Salvi, Erika; Manunta, Paolo; Mori, Yosai; Miyata, Kazunori; Higashide, Tomomi; Chihara, Etsuo; Ishiko, Satoshi; Yoshida, Akitoshi; Yanagi, Masahide; Kiuchi, Yoshiaki; Ohashi, Tsutomu; Sakurai, Toshiya; Sugimoto, Takako; Chuman, Hideki; Aihara, Makoto; Inatani, Masaru; Miyake, Masahiro; Gotoh, Norimoto; Matsuda, Fumihiko; Yoshimura, Nagahisa; Ikeda, Yoko; Ueno, Morio; Sotozono, Chie; Jeoung, Jin Wook; Sagong, Min; Park, Kyu Hyung; Ahn, Jeeyun; Cruz-Aguilar, Marisa; Ezzouhairi, Sidi M.; Rafei, Abderrahman; Chong, Yaan Fun; Ng, Xiao Yu; Goh, Shuang Ru; Chen, Yueming; Yong, Victor H. K.; Khan, Muhammad Imran; Olawoye, Olusola O.; Ashaye, Adeyinka O.; Ugbede, Idakwo; Onakoya, Adeola; Kizor-Akaraiwe, Nkiru; Teekhasaenee, Chaiwat; Suwan, Yanin; Supakontanasan, Wasu; Okeke, Suhanya; Uche, Nkechi J.; Asimadu, Ifeoma; Ayub, Humaira; Akhtar, Farah; Kosior-Jarecka, Ewa; Lukasik, Urszula; Lischinsky, Ignacio; Castro, Vania; Perez Grossmann, Rodolfo; Megevand, Gordana Sunaric; Roy, Sylvain; Dervan, Edward; Silke, Eoin; Rao, Aparna; Sahay, Priti; Fornero, Pablo; Cuello, Osvaldo; Sivori, Delia; Zompa, Tamara; Mills, Richard A.; Souzeau, Emmanuelle; Mitchell, Paul; Wang, Jie Jin; Hewitt, Alex W.; Coote, Michael; Crowston, Jonathan G.; Astakhov, Sergei Y.; Akopov, Eugeny L.; Emelyanov, Anton; Vysochinskaya, Vera; Kazakbaeva, Gyulli; Fayzrakhmanov, Rinat; Al-Obeidan, Saleh A.; Owaidhah, Ohoud; Aljasim, Leyla Ali; Chowbay, Balram; Foo, Jia Nee; Soh, Raphael Q.; Sim, Kar Seng; Xie, Zhicheng; Cheong, Augustine W. O.; Mok, Shi Qi; Soo, Hui Meng; Chen, Xiao Yin; Peh, Su Qin; Heng, Khai Koon; Husain, Rahat; Ho, Su-Ling; Hillmer, Axel M.; Cheng, Ching-Yu; Escudero-Dominguez, Francisco A.; Gonzalez-Sarmiento, Rogelio; Martinon-Torres, Frederico; Salas, Antonio; Pathanapitoon, Kessara; Hansapinyo, Linda; Wanichwecharugruang, Boonsong; Kitnarong, Naris; Sakuntabhai, Anavaj; Nguyn, Hip X.; Nguyn, Giang T. T.; Nguyn, TrNh V.; Zenz, Werner; Binder, Alexander; Klobassa, Daniela S.; Hibberd, Martin L.; Davila, Sonia; Herms, Stefan; Nothen, Markus M.; Moebus, Susanne; Rautenbach, Robyn M.; Ziskind, Ari; Carmichael, Trevor R.; Ramsay, Michele; Alvarez, Lydia; Garcia, Montserrat; Gonzalez-Iglesias, Hector; Rodriguez-Calvo, Pedro P.; Fernandez-Vega Cueto, Luis; Oguz, Cilingir; Tamcelik, Nevbahar; Atalay, Eray; Batu, Bilge; Aktas, Dilek; Kasim, Burcu; Wilson, M. Roy; Coleman, Anne L.; Liu, Yutao; Challa, Pratap; Herndon, Leon; Kuchtey, Rachel W.; Kuchtey, John; Curtin, Karen; Chaya, Craig J.; Crandall, Alan; Zangwill, Linda M.; Wong, Tien Yin; Nakano, Masakazu; Kinoshita, Shigeru; den Hollander, Anneke I.; Vesti, Eija; Fingert, John H.; Lee, Richard K.; Sit, Arthur J.; Shingleton, Bradford J.; Wang, Ningli; Cusi, Daniele; Qamar, Raheel; Kraft, Peter; Pericak-Vance, Margaret A.; Raychaudhuri, Soumya; Heegaard, Steffen; Kivela, Tero; Reis, Andre; Kruse, Friedrich E.; Weinreb, Robert N.; Pasquale, Louis R.; Haines, Jonathan L.; Thorsteinsdottir, Unnur; Jonasson, Fridbert; Allingham, R. Rand; Milea, Dan; Ritch, Robert; Kubota, Toshiaki; Tashiro, Kei; Vithana, Eranga N.; Micheal, Shazia; Topouzis, Fotis; Craig, Jamie E.; Dubina, Michael; Sundaresan, Periasamy; Stefansson, Kari; Wiggs, Janey L.; Pasutto, Francesca; Khor, Chiea Chuen |
| Contributors: |
Park, Ki Ho; Jeoung, Jin Wook; Park, Kyu Hyung |
| Publisher Information: |
Nature Publishing Group |
| Publication Year: |
2018 |
| Collection: |
Seoul National University: S-Space |
| Subject Terms: |
GENOME-WIDE ASSOCIATION; INFLAMMATORY-BOWEL-DISEASE; COMMON SEQUENCE VARIANTS; PSEUDOEXFOLIATION SYNDROME; RISK LOCI; MACULAR DEGENERATION; BLOOD-PRESSURE; SYNONYMOUS MUTATIONS; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE |
| Description: |
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 x 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 x 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. ; Y ; 1 |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
https://hdl.handle.net/10371/222600; 000404253300007; 52246 |
| DOI: |
10.1038/ng.3875 |
| Availability: |
https://hdl.handle.net/10371/222600; https://doi.org/10.1038/ng.3875 |
| Accession Number: |
edsbas.1B591D02 |
| Database: |
BASE |