The causal relationship between enlarged perivascular spaces and intracerebral hemorrhage: A 2-sample Mendelian randomization study

The genetic prediction of the causal relationship between enlarged perivascular spaces (PVS) and intracerebral hemorrhage (ICH). We performed a 2-sample Mendelian randomization (MR) study that used published data from genome-wide association studies on ICH and PVS. We primarily utilized the inverse variance weighted (IVW), MR-Egger, weighted median and weighted mode method. Sensitivity analyses included Cochran Q test, MR-Egger regression, MR-PRESSO global test and leave-one-out analysis. IVW analysis showed no statistical association between genetically predicted enlargement of hippocampal PVS (OR = 0.74, 95% CI = 0.23-2.35, P = .605), basal ganglia PVS (OR = 1.59, 95% CI = 0.64-3.95, P = .318), or white matter PVS (OR = 1.59, 95% CI = 0.64-3.95, P = .318) with the risk of ICH. The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. The sensitivity analyses did not reveal any pleiotropy or heterogeneity. The leave-one-out plots did not found any single mutation that might influence the results. Our findings indicate that there is no causal relationship between PVS enlargement and the development of ICH at the genetic level. Using PVS as a diagnostic marker might lack specificity, needed for the planning of timely diagnostic procedures in the risk populations.