Investigating the Mediating Role of Cardiometabolic Traits in the Causal Link Between SHBG Levels and Stroke Risk via Network Mendelian Randomization.

ABSTRACT: The causal nature of sex hormone-binding globulin (SHBG) in the pathogenesis of stroke remains uncertain. We explored whether SHBG levels are causally associated with stroke via cardiometabolic traits. A network two-sample Mendelian randomization (MR) study was conducted to determine the mediating roles of cardiometabolic traits in the causal effects of SHBG levels on stroke subtypes. Further two-sample MR analyses were performed to explore the inverse associations between significant cardiometabolic mediators and SHBG levels. The MR results indicated a protective effect of genetically increased SHBG levels on any stroke (odd ratio [OR] = 0.941; 95% confidence interval [CI]: 0.898, 0.984), any ischemic stroke (OR = 0.951; 95% CI: 0.922, 0.981), and small-vessel stroke (OR = 0.871; 95% CI:

SUBMITTER: Pan P 

PROVIDER: S-EPMC12293703 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature