Genetic evidence of association between family factors and the risk of stroke: A 2-sample Mendelian randomization analysis

Family factors are often related to health and mental well-being. We aimed to investigate the causal relationship between family factors and the risk of stroke using Mendelian randomization (MR). The genome-wide association study data used in this analysis was obtained from the Neale Lab, Medical Research Council Integrative Epidemiology Unit. Family factors included financial difficulties, marital separation/divorce and family relationship satisfaction, and all exposures were binary. Stroke was classified as intracerebral hemorrhage (ICH) and ischemic stroke (IS). An inverse-variance weighted method was used mainly in the MR analysis, and the weighted median and MR-Egger methods supplemented the findings. Sensitivity analyses were performed to assess the robustness and reliability of our findings. A total of 30, 11 and 28 single nucleotide polymorphisms were selected as instrumental variables to assess the causal effects of financial difficulties, marital separation/divorce, and family relationship satisfaction on the risk of ICH and IS. Our study found that financial difficulties were causally linked to an elevated risk of ICH (odds ratio [OR] = 1.014, 95% confidence interval [CI] = 1.001-1.028, P = .04), whereas no significant associations were observed with IS (OR = 1.012, 95% CI = 0.988-1.036, P = .33). Additionally, marital separation/divorce showed genetic evidence with higher ICH incidence (OR = 1.054, 95% CI = 1.009-1.101, P = .017), but no statistically significant relationships were detected with IS (OR = 1.026, 95% CI = 0.961-1.096, P = .44). There was no causal correlation of family relationship satisfaction identified with ICH (OR = 0.999, 95% CI = 0.996-1.002, P = .56) or IS (OR = 1.001, 95% CI = 0.996-1.002, P = .17). Sensitivity analyses confirmed the robustness of these findings. This study provides genetic evidence supporting a link between family factors and stroke risk. Specifically, genetic predisposition to financial difficulties and marital separation/divorce suggests a potential causal association with an increased risk of ICH.