Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci Academic Article uri icon

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.

authors

  • Aung, Tin
  • Ozaki, Mineo
  • Lee, Mei Chin
  • Schlötzer-Schrehardt, Ursula
  • Thorleifsson, Gudmar
  • Mizoguchi, Takanori
  • Igo, Robert P
  • 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
  • Järvelä, Irma
  • Schlottmann, Patricio
  • Lerner, S Fabian
  • Lamari, Hasnaa
  • Nilgün, 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 SY
  • 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, Stéphanie
  • Reynier, Pascal
  • Chichua, George
  • Tabagari, Sergo
  • Uebe, Steffen
  • Zenkel, Matthias
  • Berner, Daniel
  • Mossböck, Georg
  • Weisschuh, Nicole
  • Hoja, Ursula
  • Welge-Luessen, Ulrich-Christoph
  • Mardin, Christian
  • Founti, Panayiota
  • Chatzikyriakidou, Anthi
  • Pappas, Theofanis
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  • Lambropoulos, Alexandros
  • Ghosh, Arkasubhra
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  • Beni, Afsaneh Naderi
  • Yazdani, Shahin
  • lashay, Alireza
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  • Rolle, Teresa
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  • Paoli, Daniela
  • Salvi, Erika
  • Manunta, Paolo
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  • Miyata, Kazunori
  • Higashide, Tomomi
  • Chihara, Etsuo
  • Ishiko, Satoshi
  • Yoshida, Akitoshi
  • Yanagi, Masahide
  • Kiuchi, Yoshiaki
  • Ohashi, Tsutomu
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  • Gotoh, Norimoto
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  • Ikeda, Yoko
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  • Challa, Pratap
  • Herndon, Leon
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  • Crandall, Alan
  • Zangwill, Linda M
  • Wong, Tien Yin
  • Nakano, Masakazu
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  • Vesti, Eija
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  • Khor, Chiea Chuen

publication date

  • 2017

has subject area