Browse by author
Lookup NU author(s): Professor Heather Cordell
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
© 2024Patients with primary biliary cholangitis (PBC) commonly experience extrahepatic rheumatic diseases. However, the epidemiologic and genetic associations as well as causal relationship between PBC and these extrahepatic conditions remain undetermined. In this study, we first conducted systematic review and meta-analyses by analyzing 73 studies comprising 334,963 participants across 17 countries and found strong phenotypic associations between PBC and rheumatic diseases. Next, we utilized large-scale genome-wide association study summary data to define the shared genetic architecture between PBC and rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Sjögren's syndrome (SS). We observed significant genetic correlations between PBC and each of the four rheumatic diseases. Pleiotropy and heritability enrichment analysis suggested the involvement of humoral immunity and interferon-associated processes for the comorbidity. Of note, we identified four variants shared between PBC and RA (rs80200208), SLE (rs9843053), and SSc (rs27524, rs3873182) using cross-trait meta-analysis. Additionally, several pleotropic loci for PBC and rheumatic diseases were found to share causal variants with gut microbes possessing immunoregulatory functions. Finally, Mendelian randomization revealed consistent evidence for a causal effect of PBC on RA, SLE, SSc, and SS, but no or inconsistent evidence for a causal effect of extrahepatic rheumatic diseases on PBC. Our study reveals a profound genetic overlap and causal relationships between PBC and extrahepatic rheumatic diseases, thus providing insights into shared biological mechanisms and novel therapeutic interventions.
Author(s): Qian Q, Wu Y, Cui N, Li Y, Zhou Y, Li Y, Lian M, Xiao X, Miao Q, You Z, Wang Q, Shi Y, Cordell HJ, Timilsina S, Gershwin ME, Li Z, Ma X, Ruqi Tang
Publication type: Article
Publication status: Published
Journal: Journal of Autoimmunity
Year: 2024
Volume: 148
Print publication date: 01/09/2024
Online publication date: 26/07/2024
Acceptance date: 14/07/2024
ISSN (print): 0896-8411
ISSN (electronic): 1095-9157
Publisher: Academic Press
URL: https://doi.org/10.1016/j.jaut.2024.103289
DOI: 10.1016/j.jaut.2024.103289
Altmetrics provided by Altmetric
