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A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome.

Publication ,  Journal Article
Aung, T; Ozaki, M; Mizoguchi, T; Allingham, RR; Li, Z; Haripriya, A; Nakano, S; Uebe, S; Harder, JM; Chan, ASY; Lee, MC; Burdon, KP; Jia, L ...
Published in: Nat Genet
April 2015

Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) of 1,484 cases and 1,188 controls from Japan and followed up the most significant findings in a further 6,901 cases and 20,727 controls from 17 countries across 6 continents. We discovered a genome-wide significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (odds ratio (OR) = 1.16, P = 3.36 × 10(-11)). Although we also confirmed overwhelming association at the LOXL1 locus, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on the ancestry group (Japanese: OR(A allele) = 9.87, P = 2.13 × 10(-217); non-Japanese: OR(A allele) = 0.49, P = 2.35 × 10(-31)). Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease.

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Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

April 2015

Volume

47

Issue

4

Start / End Page

387 / 392

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Polymorphism, Single Nucleotide
  • Mice, Inbred C57BL
  • Mice
  • MCF-7 Cells
  • Japan
  • Humans
  • Hela Cells
  • HeLa Cells
  • HEK293 Cells
 

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APA
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Aung, T., Ozaki, M., Mizoguchi, T., Allingham, R. R., Li, Z., Haripriya, A., … Khor, C.-C. (2015). A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome. Nat Genet, 47(4), 387–392. https://doi.org/10.1038/ng.3226
Aung, Tin, Mineo Ozaki, Takanori Mizoguchi, R Rand Allingham, Zheng Li, Aravind Haripriya, Satoko Nakano, et al. “A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome.Nat Genet 47, no. 4 (April 2015): 387–92. https://doi.org/10.1038/ng.3226.
Aung T, Ozaki M, Mizoguchi T, Allingham RR, Li Z, Haripriya A, et al. A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome. Nat Genet. 2015 Apr;47(4):387–92.
Aung, Tin, et al. “A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome.Nat Genet, vol. 47, no. 4, Apr. 2015, pp. 387–92. Pubmed, doi:10.1038/ng.3226.
Aung T, Ozaki M, Mizoguchi T, Allingham RR, Li Z, Haripriya A, Nakano S, Uebe S, Harder JM, Chan ASY, Lee MC, Burdon KP, Astakhov YS, Abu-Amero KK, Zenteno JC, Nilgün Y, Zarnowski T, Pakravan M, Safieh LA, Jia L, Wang YX, Williams S, Paoli D, Schlottmann PG, Huang L, Sim KS, Foo JN, Nakano M, Ikeda Y, Kumar RS, Ueno M, Manabe S-I, Hayashi K, Kazama S, Ideta R, Mori Y, Miyata K, Sugiyama K, Higashide T, Chihara E, Inoue K, Ishiko S, Yoshida A, Yanagi M, Kiuchi Y, Aihara M, Ohashi T, Sakurai T, Sugimoto T, Chuman H, Matsuda F, Yamashiro K, Gotoh N, Miyake M, Astakhov SY, Osman EA, Al-Obeidan SA, Owaidhah O, Al-Jasim L, Al Shahwan S, Fogarty RA, Leo P, Yetkin Y, Oğuz Ç, Kanavi MR, Beni AN, Yazdani S, Akopov EL, Toh K-Y, Howell GR, Orr AC, Goh Y, Meah WY, Peh SQ, Kosior-Jarecka E, Lukasik U, Krumbiegel M, Vithana EN, Wong TY, Liu Y, Koch AEA, Challa P, Rautenbach RM, Mackey DA, Hewitt AW, Mitchell P, Wang JJ, Ziskind A, Carmichael T, Ramakrishnan R, Narendran K, Venkatesh R, Vijayan S, Zhao P, Chen X, Guadarrama-Vallejo D, Cheng CY, Perera SA, Husain R, Ho S-L, Welge-Luessen U-C, Mardin C, Schloetzer-Schrehardt U, Hillmer AM, Herms S, Moebus S, Nöthen MM, Weisschuh N, Shetty R, Ghosh A, Teo YY, Brown MA, Lischinsky I, Blue Mountains Eye Study GWAS Team, Wellcome Trust Case Control Consortium 2, Crowston JG, Coote M, Zhao B, Sang J, Zhang N, You Q, Vysochinskaya V, Founti P, Chatzikyriakidou A, Lambropoulos A, Anastasopoulos E, Coleman AL, Wilson MR, Rhee DJ, Kang JH, May-Bolchakova I, Heegaard S, Mori K, Alward WLM, Jonas JB, Xu L, Liebmann JM, Chowbay B, Schaeffeler E, Schwab M, Lerner F, Wang N, Yang Z, Frezzotti P, Kinoshita S, Fingert JH, Inatani M, Tashiro K, Reis A, Edward DP, Pasquale LR, Kubota T, Wiggs JL, Pasutto F, Topouzis F, Dubina M, Craig JE, Yoshimura N, Sundaresan P, John SWM, Ritch R, Hauser MA, Khor C-C. A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome. Nat Genet. 2015 Apr;47(4):387–392.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

April 2015

Volume

47

Issue

4

Start / End Page

387 / 392

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Polymorphism, Single Nucleotide
  • Mice, Inbred C57BL
  • Mice
  • MCF-7 Cells
  • Japan
  • Humans
  • Hela Cells
  • HeLa Cells
  • HEK293 Cells