| Literature DB >> 28041642 |
F David Carmona1, Augusto Vaglio2, Sarah L Mackie3, José Hernández-Rodríguez4, Paul A Monach5, Santos Castañeda6, Roser Solans7, Inmaculada C Morado8, Javier Narváez9, Marc Ramentol-Sintas7, Colin T Pease3, Bhaskar Dasgupta10, Richard Watts11, Nader Khalidi12, Carol A Langford13, Steven Ytterberg14, Luigi Boiardi15, Lorenzo Beretta16, Marcello Govoni17, Giacomo Emmi18, Francesco Bonatti19, Marco A Cimmino20, Torsten Witte21, Thomas Neumann22, Julia Holle23, Verena Schönau24, Laurent Sailler25, Thomas Papo26, Julien Haroche27, Alfred Mahr28, Luc Mouthon29, Øyvind Molberg30, Andreas P Diamantopoulos31, Alexandre Voskuyl32, Elisabeth Brouwer33, Thomas Daikeler34, Christoph T Berger35, Eamonn S Molloy36, Lorraine O'Neill36, Daniel Blockmans37, Benedicte A Lie38, Paul Mclaren39, Timothy J Vyse40, Cisca Wijmenga41, Yannick Allanore42, Bobby P C Koeleman43, Jennifer H Barrett3, María C Cid4, Carlo Salvarani15, Peter A Merkel44, Ann W Morgan3, Miguel A González-Gay45, Javier Martín46.
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.Entities:
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Year: 2016 PMID： 28041642 PMCID： PMC5223025 DOI： 10.1016/j.ajhg.2016.11.013
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025