AUTHOR=Zhang Luofei , Yu Kefu , Huo Jiping , Mei Shenghui , Zhao Zhigang , Zhu Bin TITLE=Causal relationship between spondylarthritis and stroke in a European population: a two sample Mendelian randomization study JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1253986 DOI=10.3389/fimmu.2023.1253986 ISSN=1664-3224 ABSTRACT=Background

Observational studies have found an increased risk of stroke in patients with spondyloarthritis, but the results are susceptible to reverse causality and confounders. Therefore, the study aimed to further explore the association between spondyloarthritis and different subtypes of stroke by using a two sample Mendelian randomization (MR) analysis.

Methods

Genetic instrumental variables for spondyloarthritis were identified using summary level data from a genome-wide association study involving 201,581 people. Summary statistics from the Multiancestry Genome-wide Association Study of Stroke Consortium were used to obtain genetic data on stroke. There was no sample overlap between the exposure and outcome datasets. Inverse-variance weighted was considered the primary MR method for causal analysis. Heterogeneity, pleiotropy and sensitivity analyses were performed to ensure robustness, and single nucleotide polymorphism (SNP) with potential confounders was further screened in the PhenoScanner database to better evaluate the stability of our study.

Results

One SNP (rs1065045) was excluded due to schizophrenia. After excluding SNP (rs1065045), results of the second MR analysis were slightly different from the first, which were considered as the final result: a significant positive causality between spondyloarthritis and cardioembolic stroke (OR=1.296, 95% CI:1.094-1.534, p=0.003); a possible positive causality between spondyloarthritis and any stroke (OR=1.082, 95% CI:1.016-1.152, p=0.013)/any ischemic stroke (OR=1.086, 95% CI:1.013-1.163, p=0.020); no significant/possible causality between spondyloarthritis and small vessel stroke (OR=1.168, 95% CI:0.993-1.375, p=0.061). Insufficient power may be one possible reason why a causality was not observed between spondyloarthritis in our study.

Conclusions

This study suggests that the possible causative effects of spondyloarthritis predicted by genetics on stroke may be limited to any stroke, any ischemic stroke, and cardioembolic stroke, especially the last.