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

Journal article


Publication Details

Author(s): 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 C, 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
Journal: Nature Genetics
Publication year: 2015
Volume: 47
Journal issue: 4
Pages range: 387-92
ISSN: 1061-4036


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.



FAU Authors / FAU Editors

Schlötzer-Schrehardt, Ursula apl. Prof. Dr.
Medizinische Fakultät
Uebe, Steffen Dr. rer. nat.
Humangenetisches Institut


External institutions with authors

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


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: 

Last updated on 2018-06-10 at 03:12