%0 Journal Article
%T A Genome-wide Association Study Identifies Risk Alleles in Plasminogen and P4HA2 Associated with Giant Cell Arteritis
%A Alexandre Voskuyl
%A Alfred Mahr
%A Andreas P. Diamantopoulos
%A Ann W. Morgan
%A Augusto Vaglio
%A Benedicte A. Lie
%A Bhaskar Dasgupta
%A Bobby P.C. Koeleman
%A Carlo Salvarani
%A Carol A. Langford
%A Christoph T. Berger
%A Cisca Wijmenga
%A Colin T. Pease
%A Daniel Blockmans
%A Eamonn S. Molloy
%A Elisabeth Brouwer
%A Francesco Bonatti
%A Giacomo Emmi
%A Inmaculada C. Morado
%A Javier Mart¨ªn
%A Javier Narv¨¢ez
%A Jennifer H. Barrett
%A Jos¨¦ Hern¨¢ndez-Rodr¨ªguez
%A Julia Holle
%A Julien Haroche
%A Laurent Sailler
%A Lorenzo Beretta
%A Lorraine O¡¯Neill
%A Luc Mouthon
%A Luigi Boiardi
%A Marc Ramentol-Sintas
%A Marcello Govoni
%A Marco A. Cimmino
%A Mar¨ªa C. Cid
%A Miguel A. Gonz¨¢lez-Gay
%A Nader Khalidi
%A Paul A. Monach
%A Paul Mclaren
%A Peter A. Merkel
%A Richard Watts
%A Roser Solans
%A Santos Casta£¿eda
%A Sarah L. Mackie
%A Spanish CGA Group
%A Steven Ytterberg
%A Thomas Daikeler
%A Thomas Neumann
%A Thomas Papo
%A Timothy J. Vyse
%A Torsten Witte
%A UKGCA Consortium
%A Vasculitis Clinical Research Consortium
%A Verena Sch£¿nau
%A Yannick Allanore
%A £¿yvind Molberg
%J Archive of "American Journal of Human Genetics".
%D 2017
%R 10.1016/j.ajhg.2016.11.013
%X Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analyzed in 2,134 case subjects and 9,125 unaffected individuals from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, p = 1.94 ¡Á 10£¿54, per-allele OR = 1.79; and rs9275592, p = 1.14 ¡Á 10£¿40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, p = 1.23 ¡Á 10£¿10, OR = 1.28; and rs128738, p = 4.60 ¡Á 10£¿9, OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5223025/