Ischemic Stroke and Cerebral Microbleeds: A Two-Sample Bidirectional Mendelian Randomization Study

Abstract Introduction Recent observational studies have reported the association between ischemic stroke (IS) and cerebral microbleeds (CMBs). Whether this reflects a causal association remains to be established. Herein, we adopted a two-sample bidirectional Mendelian randomization (MR) analysis to comprehensively evaluate the causal association of IS and CMBs. Methods The summary-level genome-wide association studies (GWASs) data of IS were obtained from the GIGASTROKE consortium (62,100 European ancestry cases and 1,234,808 European ancestry controls). All IS cases could be further divided into large-vessel atherosclerosis stroke (LVS, n = 6399), cardio-embolic stroke (CES, n = 10,804) and small-vessel occlusion stroke (SVS, n = 6811). Meanwhile, we used publicly available summary statistics from published GWASs of CMBs (3556 of the 25,862 European participants across 2 large initiatives). A bidirectional MR analysis was conducted using inverse-variance weighting (IVW) as the major outcome, whereas MR-Egger and weighted median (WM) were used to complement the IVW estimates as they can provide more robust estimates in a broader set of scenarios but are less efficient (wider CIs). A Bonferroni-corrected threshold of p