Title

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

Authors

Tin Aung
Mineo Ozaki
Takanori Mizoguchi
R Rand Allingham
Zheng Li
Aravind Haripriya
Satoko Nakano
Steffen Uebe
Jeffrey M. Harder, The Jackson LaboratoryFollow
Anita S Y Chan
Mei Chin Lee
Kathryn P Burdon
Yury S Astakhov
Khaled K Abu-Amero
Juan C Zenteno
Yildirim Nilgün
Tomasz Zarnowski
Mohammad Pakravan
Leen Abu Safieh
Liyun Jia
Ya Xing Wang
Susan Williams
Daniela Paoli
Patricio G Schlottmann
Lulin Huang
Kar Seng Sim
Jia Nee Foo
Masakazu Nakano
Yoko Ikeda
Rajesh S Kumar
Morio Ueno
Shin-Ichi Manabe
Ken Hayashi
Shigeyasu Kazama
Ryuichi Ideta
Yosai Mori
Kazunori Miyata
Kazuhisa Sugiyama
Tomomi Higashide
Etsuo Chihara
Kenji Inoue
Satoshi Ishiko
Akitoshi Yoshida
Masahide Yanagi
Yoshiaki Kiuchi
Makoto Aihara
Tsutomu Ohashi
Toshiya Sakurai
Takako Sugimoto
Hideki Chuman
Fumihiko Matsuda
Kenji Yamashiro
Norimoto Gotoh
Masahiro Miyake
Sergei Y Astakhov
Essam A Osman
Saleh A Al-Obeidan
Ohoud Owaidhah
Leyla Al-Jasim
Sami Al Shahwan
Rhys A Fogarty
Paul Leo
Yaz Yetkin
Çilingir Oğuz
Mozhgan Rezaei Kanavi
Afsaneh Nederi Beni
Shahin Yazdani
Evgeny L Akopov
Kai-Yee Toh
Gareth R. Howell, The Jackson LaboratoryFollow
Andrew C Orr
Yufen Goh
Wee Yang Meah
Su Qin Peh
Ewa Kosior-Jarecka
Urszula Lukasik
Mandy Krumbiegel
Eranga N Vithana
Tien Yin Wong
Yutao Liu
Allison E Ashley Koch
Pratap Challa
Robyn M Rautenbach
David A Mackey
Alex W Hewitt
Paul Mitchell
Jie Jin Wang
Ari Ziskind
Trevor Carmichael
Rangappa Ramakrishnan
Kalpana Narendran
Rangaraj Venkatesh
Saravanan Vijayan
Peiquan Zhao
Xueyi Chen
Dalia Guadarrama-Vallejo
Ching Yu Cheng
Shamira A Perera
Rahat Husain
Su-Ling Ho
Ulrich-Christoph Welge-Luessen
Christian Mardin
Ursula Schloetzer-Schrehardt
Axel M Hillmer
Stefan Herms
Susanne Moebus
Markus M Nöthen
Nicole Weisschuh
Rohit Shetty
Arkasubhra Ghosh
Yik Ying Teo
Matthew A Brown
Ignacio Lischinsky
Jonathan G Crowston
Michael Coote
Bowen Zhao
Jinghong Sang
Nihong Zhang
Qisheng You
Vera Vysochinskaya
Panayiota Founti
Anthoula Chatzikyriakidou
Alexandros Lambropoulos
Eleftherios Anastasopoulos
Anne L Coleman
M Roy Wilson
Douglas J Rhee
Jae Hee Kang
Inna May-Bolchakova
Steffen Heegaard
Kazuhiko Mori
Wallace L M Alward
Jost B Jonas
Liang Xu
Jeffrey M Liebmann
Balram Chowbay
Elke Schaeffeler
Matthias Schwab
Fabian Lerner
Ningli Wang
Zhenglin Yang
Paolo Frezzotti
Shigeru Kinoshita
John H Fingert
Masaru Inatani
Kei Tashiro
André Reis
Deepak P Edward
Louis R Pasquale
Toshiaki Kubota
Janey L Wiggs
Francesca Pasutto
Fotis Topouzis
Michael Dubina
Jamie E Craig
Nagahisa Yoshimura
Periasamy Sundaresan
Simon W M John, The Jackson LaboratoryFollow
Robert Ritch
Michael A Hauser
Chiea-Chuen Khor

Document Type

Article

Publication Date

4-2015

JAX Source

Nat Genet 2015 Apr; 47(4):387-92.

PMID

25706626

Grant

EY11721

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: 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. Nat Genet 2015 Apr; 47(4):387-92.