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

Francisco David Carmona, Augusto Vaglio, Sarah L. Mackie, José Hernández-Rodríguez, Paul A. Monach, Santos Castañeda, Roser Solans, Inmaculada C. Morado, Francisco Javier Narváez, Marc Ramentol-Sintas, Colin T. Pease, Bhaskar Dasgupta, Richard Watts, Nader A. Khalidi, Carol A. Langford, Steven R. Ytterberg, Luigi Boiardi, Lorenzo Beretta, Marcello Govoni, Giacomo EmmiFrancesco Bonatti, Marco A. Cimmino, Torsten Witte, Thomas Neumann, Julia Holle, Verena Schönau, Laurent Sailler, Thomas Papo, Julien Haroche, Alfred Mahr, Luc Mouthon, Øyvind Molberg, Andreas P. Diamantopoulos, Alexandre E. Voskuyl, Elisabeth Brouwer, Thomas Daikeler, Christoph T. Berger, Eamonn S. Molloy, Lorraine O'Neill, Daniel Blockmans, Benedicte A. Lie, Paul J McLaren, Timothy J. Vyse, Cisca Wijmenga, Yannick Allanore, Bobby P.C. Koeleman, José Luis Callejas-Rubio, Luis Caminal-Montero, Marc Corbera-Bellalta, Eugenio de Miguel, , , , , ,

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)64-74
Number of pages11
JournalAmerican Journal of Human Genetics
Issue number1
Publication statusPublished - 5 Jan 2017


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