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


Aung, T and Ozaki, M and Mizoguchi, T and Allingham, RR and Haripriya, A and Nakano, S and Uebe, S and Harder, JM and Chan, AS and Lee, MC and Burdon, KP and Astakhov, YS and Abu-Amero, KK and Zenteno, JC and Nilgun, Y and Zarnowski, T and Pakravan, M and Safieh, LA and Jia, L and Wang, YX and Williams, S and Paoli, D and Schlottmann, PG and Huang, L and Sim, KS and Foo, JN and Nakano, M and Ikeda, Y and Kumar, RS and Ueno, M and Manabe, SI and Hayashi, K and Kazama, S and Ideta, R and Mori, Y and Miyata, K and Sugiyama, K and Higashide, T and Chihara, E and Inoue, K and Ishiko, S and Yoshida, A and Yanagi, M and Kiuchi, Y and Aihara, M and Ohashi, T and Sakurai, T and Sugimoto, T and Chuman, H and Matsuda, F and Yamashiro, K and Gotoh, N and Miyake, M and Astakhov, SY and Osman, EA and Al-Obeidan, SA and Owaidhah, O and Al-Jasim, L and Shahwan, SA and Fogarty, RA and Leo, P and Yetkin, Y and Oguz, C and Kanavi, MR and Beni, AN and Yazdani, S and Akopov, EL and Toh, KY and Howell, GR and Orr, AC and Goh, Y and Meah, WY and Peh, SQ and Kosior-Jarecka, E and Lukasik, U and Krumbiegel, M and Vithana, EN and Wong, TY and Liu, Y and Koch, AE and Challa, P and Rautenbach, RM and Mackey, DA and Hewitt, AW and Mitchell, P and Wang, JJ and Ziskind, A and Carmichael, T and Ramakrishnan, R and Narendran, K and Venkatesh, R and Vijayan, S and Zhao, P and Chen, X and Guadarrama-Vallejo, D and Cheng, CY and Perera, SA and Husain, R and Welge-Luessen, UC and Mardin, C and Ghosh, A and Teo, YY and Brown, MA and Lischinsky, I and Crowston, JG and Coote, M and Zhao, B and Sang, J and Zhang, N and You, Q and Vysochinskaya, V and Founti, P and Chatzikyriakidou, A and Lambropoulos, A and Anastasopoulos, E and Coleman, AL and Wilson, MR and Rhee, DJ and Kang, JH and May-Bolchakova, I and Heegaard, S and Mori, K and Alward, WL and Jonas, JB and Xu, L and Liebmann, JM and Chowbay, B and Schaeffeler, E and Schwab, M and Lerner, F and Wang, N and Yang, Z and Frezzotti, P and Kinoshita, S and Fingert, JH and Inatani, M and Tashiro, K and Reis, A and Edward, DP and Pasquale, LR and Kubota, T and Wiggs, JL and Pasutto, F and Topouzis, F and Dubina, M and Craig, JE and Yoshimura, N and Sundaresan, P and John, SW and Ritch, R and Hauser, MA and Khor, CC and Schloetzer-Schrehardt, U and Hillmer, AM and Herms, S and Moebus, S and Nothen, MM and Weisschuh, N and Shetty, R and Zheng, L and Ho, S-U, Blue Mountains Eye Study GWAS Team; Wellcome Trust Case Control Consortium 2, A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome, Nature Genetics, 47, (4) pp. 387-392. ISSN 1061-4036 (2015) [Refereed Article]

Copyright Statement

Coptyright 2015 Nature America, Inc.

DOI: doi:10.1038/ng.3226


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: ORA allele = 9.87, P = 2.13 10−217; non-Japanese: ORA 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.

Item Details

Item Type:Refereed Article
Keywords:pseudoexfoliation, glaucoma, risk profile, GWAS
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Burdon, KP (Professor Kathryn Burdon)
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:99161
Year Published:2015
Web of Science® Times Cited:64
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-03-16
Last Modified:2017-11-07

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