TY - JOUR
T1 - A Genome-wide Association Study Identifies Risk Alleles in Plasminogen and P4HA2 Associated with Giant Cell Arteritis
AU - Spanish CGA Group
AU - UKGCA Consortium
AU - Vasculitis Clinical Research Consortium
AU - UKGCA Consortium
AU - Vasculitis Clinical Research Consortium
AU - Vasculitis Clinical Research Consortium
AU - Carmona, F. David
AU - Vaglio, Augusto
AU - Mackie, Sarah L.
AU - Hernández-Rodríguez, José
AU - Monach, Paul A.
AU - Castañeda, Santos
AU - Solans, Roser
AU - Morado, Inmaculada C.
AU - Narváez, Javier
AU - Ramentol-Sintas, Marc
AU - Pease, Colin T.
AU - Dasgupta, Bhaskar
AU - Watts, Richard
AU - Khalidi, Nader
AU - Langford, Carol A.
AU - Ytterberg, Steven
AU - Boiardi, Luigi
AU - Beretta, Lorenzo
AU - Govoni, Marcello
AU - Emmi, Giacomo
AU - Bonatti, Francesco
AU - Cimmino, Marco A.
AU - Witte, Torsten
AU - Neumann, Thomas
AU - Holle, Julia
AU - Schönau, Verena
AU - Sailler, Laurent
AU - Papo, Thomas
AU - Haroche, Julien
AU - Mahr, Alfred
AU - Mouthon, Luc
AU - Molberg, Øyvind
AU - Diamantopoulos, Andreas P.
AU - Voskuyl, Alexandre
AU - Brouwer, Elisabeth
AU - Daikeler, Thomas
AU - Berger, Christoph T.
AU - Molloy, Eamonn S.
AU - O'Neill, Lorraine
AU - Blockmans, Daniel
AU - Lie, Benedicte A.
AU - Mclaren, Paul
AU - Vyse, Timothy J.
AU - Wijmenga, Cisca
AU - Allanore, Yannick
AU - Koeleman, Bobby P.C.
AU - Callejas, José Luis
AU - Caminal-Montero, Luis
AU - Corbera-Bellalta, Marc
AU - Seo, Philip
N1 - Funding Information:
The UKGCA Consortium has been funded by Research into Ageing and The Wellcome Trust and is currently supported by the National Institute for Health Research (Clinician Scientist Fellowship for S.L.M., Leeds Musculoskeletal Biomedical Research Unit [A.W.M. and J.H.B.], and Diagnostic Evidence Co-operative [A.W.M.]), the Medical Research Council, and the Ann Wilks Memorial Fund. This article presents independent research funded in part by the National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR, or the Department of Health.
Publisher Copyright:
© 2017 American Society of Human Genetics
PY - 2017/1/5
Y1 - 2017/1/5
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajhg.2016.11.013
DO - 10.1016/j.ajhg.2016.11.013
M3 - Article
C2 - 28041642
AN - SCOPUS:85009373443
SN - 0002-9297
VL - 100
SP - 64
EP - 74
JO - American journal of human genetics
JF - American journal of human genetics
IS - 1
ER -