Stroke and Myocardial Infarction: A Bidirectional Mendelian Randomization Study

Wenxian Sun; Luyang Zhang; Weishi Liu; Mengke Tian; Xin Wang; Jing Liang; Yuying Wang; Lan Ding; Lulu Pei; Jie Lu; Yuming Xu; Bo Song

doi:10.2147/IJGM.S337681

Stroke and Myocardial Infarction: A Bidirectional Mendelian Randomization Study

Int J Gen Med. 2021 Dec 9:14:9537-9545. doi: 10.2147/IJGM.S337681. eCollection 2021.

Authors

Wenxian Sun¹, Luyang Zhang¹, Weishi Liu¹, Mengke Tian¹, Xin Wang¹, Jing Liang¹, Yuying Wang¹, Lan Ding¹, Lulu Pei¹, Jie Lu², Yuming Xu¹, Bo Song¹

Affiliations

¹ Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China.
² Department of Epidemiology and Health Statistics College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China.

Abstract

Background: Stroke and myocardial infarction (MI) are associated with each other, as demonstrated in observational studies. However, it is unclear whether this relationship is causal, and the purpose of this study was to explore the bidirectional causality between stroke and MI.

Methods: Causality between stroke and MI was assessed using two-sample Mendelian randomization (MR). All genetic instruments related to stroke (40,585 cases; 406,111 controls) and MI (43,676 cases; 128,199 controls) were derived from large published genome-wide association study. The MR analysis was calculated with inverse-variance weighting, MR-Egger, weighted mode, weighted median, and simple mode methods, and sensitivity analyses are used to detect the heterogeneity or pleiotropy.

Results: Genetically predicted large-artery stroke (LAS) was causally related to higher odds of MI (odds ratio [OR] = 1.13, 95% confidence interval [CI]: 1.06-1.20, p = 1.0×10^-4), and the causal effect of LAS on MI was significantly weakened (OR = 1.09, 95% CI: 1.02-1.17, p = 0.017) after excluding the multipotent single-nucleotide polymorphisms (SNPs). MI phenotypes were genetically correlated with all ischemic strokes (OR = 1.15, 95% CI: 1.03-1.28, p = 0.013) and LAS (OR = 1.39, 95% CI: 1.14-1.71, p = 0.001); but a causal effect of MI on all ischemic strokes (OR = 1.00, 95% CI: 0.95-1.28, p = 0.219) and LAS (OR = 1.26, 95% CI: 0.93-1.69, p = 0.130) was not observed after excluding the multipotent SNPs.

Conclusion: This MR analysis provides evidence to support the causal effect of LAS subtype on MI, and some factors act as confiding factors whereas others may act as mediators.

Keywords: causal inference; epidemiologic methods; genome-wide association study; large-artery stroke; single-nucleotide polymorphism.

Grants and funding

This research was supported by the National Key Research and Development Program, Major Chronic Non-Communicable Disease Prevention and Control Research Key Special Project (2017YFC1308202), and Henan Provincial Medical Science and Technology Research Plan (SBGJ2018031).