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A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome
journal contributionposted on 2023-05-18, 08:30 authored by Aung, T, Ozaki, M, Mizoguchi, T, Allingham, RR, Haripriya, A, Nakano, S, Uebe, S, Harder, JM, Chan, AS, Lee, MC, Kathryn BurdonKathryn Burdon, Astakhov, YS, Abu-Amero, KK, Zenteno, JC, Nilgun, 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, SI, 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, Shahwan, SA, Fogarty, RA, Leo, P, Yetkin, Y, Oguz, C, Kanavi, MR, Beni, AN, Yazdani, S, Akopov, EL, Toh, KY, Howell, GR, Orr, AC, Goh, Y, Meah, WY, Peh, SQ, Kosior-Jarecka, E, Lukasik, U, Krumbiegel, M, Vithana, EN, Wong, TY, Liu, Y, Koch, AE, Challa, P, Rautenbach, RM, Mackey, DA, Alexander HewittAlexander Hewitt, 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, Welge-Luessen, UC, Mardin, C, Ghosh, A, Teo, YY, Brown, MA, Lischinsky, I, 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, WL, 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, SW, Ritch, R, Hauser, MA, Khor, CC, Schloetzer-Schrehardt, U, Hillmer, AM, Herms, S, Moebus, S, Nothen, MM, Weisschuh, N, Shetty, R, Zheng, L, Ho, S-U
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.
Publication titleNature Genetics
Department/SchoolMenzies Institute for Medical Research
PublisherNature Publishing Group
Place of publication345 Park Ave South, New York, USA, Ny, 10010-1707
Rights statementCoptyright 2015 Nature America, Inc.