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

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, Nilguen Y, Zarnowski T, Pakravan M, Abu Safieh L, 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, Al Shahwan S, 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 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 SL, Welge-Lüssen UC, Mardin CY, Schlötzer-Schrehardt U, Hillmer AM, Herms S, Moebus S, Noethen MM, Weisschuh N, Shetty R, 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 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 CC (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Book Volume: 47

Pages Range: 387-92

Journal Issue: 4

DOI: 10.1038/ng.3226

Abstract

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.

Authors with CRIS profile

Involved external institutions

Singapore National Eye Centre (SNEC) Singapore (SG) Tan Tock Seng Hospital Singapore (SG) University of Electronic Science and Technology of China (UESTC) / 电子科技大学 China (CN) Università degli Studi di Siena (UNISI) / University of Siena Italy (IT) Kyoto Prefectural University of Medicine / 京都府立医科大学 Japan (JP) University of Iowa United States (USA) (US) University of Fukui / 福井大学 Japan (JP) King Khaled Eye Specialist Hospital Saudi Arabia (SA) Harvard University United States (USA) (US) Oita University / 大分大学 Japan (JP) Aristotle University of Thessaloniki Greece (GR) First Pavlov State Medical University of St. Petersburg Russian Federation (RU) Flinders University Australia (AU) Kyoto University / 京都大学 Kyōto daigaku Japan (JP) Aravind Medical Research Foundation India (IN) Howard Hughes Medical Institute United States (USA) (US) New York Eye and Ear Infirmary of Mount Sinai United States (USA) (US) Duke University United States (USA) (US) University of Sydney (USYD) Australia (AU) Narayana Nethralaya Eye Hospital India (IN) Hayashi Eye Hospital Japan (JP) Shinjo Eye Hospital Japan (JP) Ideta Eye Hospital Japan (JP) Miyata Eye Hospital Japan (JP) Ozaki Eye Hospital Japan (JP) Mizoguchi Eye Hospital Japan (JP) Genome Institute of Singapore Singapore (SG) Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) Universität Duisburg-Essen (UDE) Germany (DE) Universitätsklinikum Tübingen Germany (DE) Xinjiang Medical University (XMU) / 新疆医科大学 China (CN) Eye Center Lischinsky Argentina (AR) King Saud University (KSU) / جامعة الملك سعود‎‎ Saudi Arabia (SA) Institute of Ophthalmology Foundation Conde de Valenciana Private Assistance (IPA) Instituto de Oftalmología Fundación de Asistencia Privada Conde de Valenciana (IAP) Mexico (MX) Eskişehir Osmangazi Üniversitesi Turkey (TR) Medical University of Lublin / Uniwersytet Medyczny w Lublinie Poland (PL) Shahid Beheshti University of Medical Sciences Iran, Islamic Republic of (IR) Capital University of Medical Sciences / 首都医科大学 China (CN) University of the Witwatersrand (WITS) South Africa (ZA) Monfalcone Hospital Italy (IT) Kanazawa University / 金沢大学 Japan (JP) Sensho-kai Eye Institute Japan (JP) Inouye Eye Hospital Japan (JP) Asahikawa Medical University Japan (JP) Hiroshima University Japan (JP) Yotsuya Shirato Eye Clinic Japan (JP) Tane Memorial Eye Hospital Japan (JP) University of Miyazaki / 宮崎大学 Japan (JP) University of Queensland Australia (AU) Dalhousie University Canada (CA) University of Stellenbosch / Universiteit van Stellenbosch South Africa (ZA) University of Western Australia (UWA) Australia (AU) University of Tasmania (UTAS) Australia (AU) Shanghai Jiao Tong University / 上海交通大学 China (CN) The University of Melbourne Australia (AU) St. Petersburg Academic University Russian Federation (RU) University of California Los Angeles (UCLA) United States (USA) (US) Wayne State University (WSU) United States (USA) (US) Brigham and Women's Hospital (BWH) United States (USA) (US) Bégin Military Teaching Hospital / Hôpital d'instruction des armées Bégin France (FR) University of Copenhagen Denmark (DK) Ruprecht-Karls-Universität Heidelberg Germany (DE) New York University (NYU) United States (USA) (US) National Cancer Centre Singapore (NCCS) Singapore (SG) Robert-Bosch-Krankenhaus Germany (DE) Centro de Ojos Buenos Aires Argentina (AR)

How to cite

APA:

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. Nature Genetics, 47(4), 387-92. https://dx.doi.org/10.1038/ng.3226

MLA:

Aung, Tin, et al. "A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome." Nature Genetics 47.4 (2015): 387-92.

BibTeX: Download