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Genetic Liability to Rheumatoid Arthritis in Relation to Coronary Artery Disease and Stroke Risk
Author(s) -
Yuan Shuai,
Carter Paul,
Mason Amy M.,
Yang Fangkun,
Burgess Stephen,
Larsson Susanna C.
Publication year - 2022
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.42239
Subject(s) - mendelian randomization , medicine , odds ratio , coronary artery disease , stroke (engine) , genome wide association study , confidence interval , rheumatoid arthritis , cardiology , intracerebral hemorrhage , single nucleotide polymorphism , subarachnoid hemorrhage , genotype , genetics , mechanical engineering , genetic variants , gene , engineering , biology
Objective To assess the causality of the associations of rheumatoid arthritis (RA) with coronary artery disease (CAD) and stroke using the Mendelian randomization approach. Methods Independent single‐nucleotide polymorphisms strongly associated with RA (n = 70) were selected as instrumental variables from a genome‐wide association meta‐analysis including 14,361 RA patients and 43,923 controls of European ancestry. Summary‐level data for CAD, all stroke, any ischemic stroke and its subtypes, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage were obtained from meta‐analyses of genetic studies, international genetic consortia, the UK Biobank, and the FinnGen consortium. We obtained summary‐level data for common cardiovascular risk factors and related inflammatory biomarkers to assess possible mechanisms. Results Genetic liability to RA was associated with an increased risk of CAD and ICH. For a 1‐unit increase in log odds of RA, the combined odds ratios were 1.02 (95% confidence interval [1.01, 1.03]; P = 0.003) for CAD and 1.05 (95% confidence interval [1.02, 1.08]; P = 0.001) for ICH. Genetic liability to RA was associated with increased levels of tumor necrosis factor and C‐reactive protein (CRP). The association with CAD was attenuated after adjustment for genetically predicted CRP levels. There were no associations of genetic liability to RA with the other studied outcomes. Conclusion This study found that genetic liability to RA was associated with an increased risk of CAD and ICH and that the association with CAD might be mediated by CRP. The heightened cardiovascular risk should be actively monitored and managed in RA patients, and this may include dampening systemic inflammation.