A Genome-wide Association Study Identifies Risk Alleles in Plasminogen and P4HA2 Associated with Giant Cell Arteritis

Carmona, F. David and Vaglio, Augusto and Mackie, Sarah L. and Hernández-Rodríguez, José and Monach, Paul A. and Castañeda, Santos and Solans, Roser and Morado, Inmaculada C. and Narváez, Javier and Ramentol-Sintas, Marc and Pease, Colin T. and Dasgupta, Bhaskar and Watts, Richard and Khalidi, Nader and Langford, Carol A. and Ytterberg, Steven and Boiardi, Luigi and Beretta, Lorenzo and Govoni, Marcello and Emmi, Giacomo and Bonatti, Francesco and Cimmino, Marco A. and Witte, Torsten and Neumann, Thomas and Holle, Julia and Schönau, Verena and Sailler, Laurent and Papo, Thomas and Haroche, Julien and Mahr, Alfred and Mouthon, Luc and Molberg, Øyvind and Diamantopoulos, Andreas P. and Voskuyl, Alexandre and Brouwer, Elisabeth and Daikeler, Thomas and Berger, Christoph T. and Molloy, Eamonn S. and O'Neill, Lorraine and Blockmans, Daniel and Lie, Benedicte A. and Mclaren, Paul and Vyse, Timothy J. and Wijmenga, Cisca and Allanore, Yannick and Koeleman, Bobby P. C. and Spanish CGA Group, and Ukgca Consortium, and Vasculitis Clinical Research Consortium, and Barrett, Jennifer H. and Cid, María C. and Salvarani, Carlo and Merkel, Peter A. and Morgan, Ann W. and González-Gay, Miguel A. and Martín, Javier. (2017) A Genome-wide Association Study Identifies Risk Alleles in Plasminogen and P4HA2 Associated with Giant Cell Arteritis. American journal of human genetics, 100 (1). pp. 64-74.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/61291/

Downloads: Statistics Overview

Abstract

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 × 10-54, per-allele OR = 1.79; and rs9275592, p = 1.14 × 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 × 10-10, OR = 1.28; and rs128738, p = 4.60 × 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.

Faculties and Departments:	03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Translational Immunology (Berger)
UniBasel Contributors:	Berger, Christoph T.
Item Type:	Article, refereed
Article Subtype:	Research Article
ISSN:	1537-6605
Note:	Publication type according to Uni Basel Research Database: Journal article
Related URLs:	Document
Identification Number:	doi: 10.1016/j.ajhg.2016.11.013 pmid: 28041642
Last Modified:	24 Apr 2020 09:42
Deposited On:	24 Apr 2020 09:42

Repository Staff Only: item control page