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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
A Genome-wide Association Study Identifies Risk Alleles in Plasminogen and P4HA2 Associated with Giant Cell Arteritis
American Journal of Human Genetics, Volume 100, No. 1, Year 2017
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Description
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. © 2017 American Society of Human Genetics
Authors & Co-Authors
Carmona, Francisco David
Spain, Madrid
Consejo Superior de Investigaciones Científicas
Spain, Granada
Universidad de Granada
MacKie, Sarah L.
United Kingdom, Leeds
Leeds Teaching Hospitals Nhs Trust
Hernández-Rodríguez, J.
Spain, Barcelona
Institut D'investigacions Biomèdiques August pi I Sunyer - Idibaps
Castañeda, Santos
Spain, Madrid
Hospital Universitario de la Princesa
Solans-Laqué, Roser
Spain, Barcelona
Hospital Universitari Vall D'hebron
Pease, Colin Thomas
United Kingdom, Leeds
Leeds Teaching Hospitals Nhs Trust
Dasgupta, Bhaskar
United Kingdom, Southend-on-sea
Mid and South Essex Nhs Foundation Trust
Watts, Richard A.
United Kingdom, Colchester
East Suffolk and North Essex Nhs Foundation Trust
Khalidi, Nader A.
Canada, Hamilton
Mcmaster University
Boiardi, Luigi
Italy, Reggio Emilia
Azienda Ospedaliera Santa Maria Nuova Di Reggio Emilia
Beretta, Lorenzo
Italy, Milan
Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico
Govoni, Marcello
Italy, Ferrara
University of Ferrara
Emmi, Giacomo
Italy, Florence
Università Degli Studi Di Firenze
Cimmino, Marco Amedeo
Italy, Genoa
Università Degli Studi Di Genova
Witte, Torsten
Germany, Hannover
Hannover Medical School
Sailler, Laurent J.
France, Toulouse
Cerpop - Centre D'epidémiologie et de Recherche en Santé Des Populations
Papo, Thomas
France, Paris
Université Paris Cité
Haroche, Julien
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Mouthon, Luc
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Diamantopoulos, Andreas P.
Unknown Affiliation
Voskuyl, Alexandre E.
Netherlands, Amsterdam
Amsterdam Umc - Vrije Universiteit Amsterdam
Brouwer, Elisabeth J.
Netherlands, Groningen
Rijksuniversiteit Groningen
Daikeler, Thomas D.
Switzerland, Basel
Universitätsspital Basel
Berger, Christoph Tobias
Switzerland, Basel
Universitätsspital Basel
McLaren, Paul J.
Switzerland, Lausanne
Sib Swiss Institute of Bioinformatics
Vyse, Timothy J.
United Kingdom, London
King's College London
Wijmenga, Cisca
Netherlands, Groningen
Universitair Medisch Centrum Groningen
Allanore, Yannick
France, Paris
Hopital Cochin Ap-hp
Koeleman, Bobby P.C.
Netherlands, Utrecht
University Medical Center Utrecht
Callejas-Rubio, José Luís
Unknown Affiliation
Caminal-Montero, Luis
Unknown Affiliation
Gómez-Vaquero, Carmen
Unknown Affiliation
Martı́nez-Taboada, Víctor Manuel
Unknown Affiliation
Miranda-Filloy, José Alberto
Unknown Affiliation
Ortego-Centeno, Norberto
Unknown Affiliation
Prieto-González, Sergio
Unknown Affiliation
Raya Álvarez, Enriqué G.
Unknown Affiliation
Sánchez-Martín, Julio
Unknown Affiliation
Unzurrunzaga, Ainhoa
Unknown Affiliation
Isaacs, John D.
Unknown Affiliation
McHugh, N. J.
Unknown Affiliation
Patel, Yusuf I.
Unknown Affiliation
Nandi, Pradip K.
Unknown Affiliation
Li, Charles
Unknown Affiliation
Mollan, Susan Patricia
Unknown Affiliation
Hollywood, Jane
Unknown Affiliation
Robinson, James I.
Unknown Affiliation
Morgan, Michael D.L.
Unknown Affiliation
Taylor, John C.
Unknown Affiliation
Hoffman, Gary S.
Unknown Affiliation
Pagnoux, Christian
Unknown Affiliation
Spiera, Robert F.
Unknown Affiliation
Weisman, Michael H.
Unknown Affiliation
Barrett, J. H.
United Kingdom, Leeds
Leeds Teaching Hospitals Nhs Trust
Cid, Maria C.
Spain, Barcelona
Institut D'investigacions Biomèdiques August pi I Sunyer - Idibaps
Salvarani, Carlo
Italy, Reggio Emilia
Azienda Ospedaliera Santa Maria Nuova Di Reggio Emilia
Morgan, Ann W.
United Kingdom, Leeds
Leeds Teaching Hospitals Nhs Trust
González-Gay, Miguel Ángel
Spain, Santander
Universidad de Cantabria
Martin, Javier
Spain, Madrid
Consejo Superior de Investigaciones Científicas
Statistics
Citations: 59
Authors: 59
Affiliations: 42
Identifiers
Doi:
10.1016/j.ajhg.2016.11.013
ISSN:
00029297
Research Areas
Cancer
Genetics And Genomics
Study Design
Cohort Study