Carmona, DF, Vaglio, A, Mackie, SL orcid.org/0000-0003-2483-5873 et al. (53 more authors) (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. ISSN 0002-9297
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 analysed in 2,134 cases and 9,125 unaffected controls from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, P = 1.94E-54, per-allele OR = 1.79; and rs9275592, P = 1.14E-40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, P = 1.23E-10, OR = 1.28; and rs128738, P = 4.60E-09, 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | �© 2017, American Society of Human Genetics. This is an author produced version of a paper published in American Journal of Human Genetics. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 22 Nov 2016 12:28 |
Last Modified: | 20 Jun 2021 08:38 |
Published Version: | https://doi.org/10.1016/j.ajhg.2016.11.013 |
Status: | Published |
Publisher: | Elsevier (Cell Press) |
Identification Number: | 10.1016/j.ajhg.2016.11.013 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:108046 |
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