The role of leptin in ischemic stroke and its subtypes: A Mendelian randomization study.

Background And Aims: Observational studies have suggested a relationship between leptin and risk of stroke. However, evidence for the association remains inconsistent, and whether the association reflects a causal relationship remains to be established. To clarify this relationship, we adopted a two-sample Mendelian randomization (MR) analysis to investigate whether leptin plays a causal role in the risk of stroke and its subtypes.

Methods And Results: Five independent single-nucleotide polymorphisms (SNPs) associated with the leptin level from genome-wide association studies (GWASs) of European individuals were selected. We performed an MR analysis using the inverse-variance-weighted (IVW) as primary method to examine the causal effects of leptin on ischemic stroke (IS). Moreover, MR-Egger intercept and Cochran's Q statistic were also performed to detect the pleiotropy or heterogeneity of our MR results. Genetically predicted circulating leptin level was not associated with ischemic stroke [odds ratio (OR): 1.48, 95% confidence interval (CI): 0.78-2.8, P = 0.22], large artery stroke (OR: 1.44, 95% CI: 0.39-5.25, P = 0.57), cardioembolic stroke (OR:1.33, 95% CI: 0.55-3.22, P = 0.52), and small vessel stroke (OR: 1.48, 95% CI: 0.39-5.63, P = 0.56) using the IVW method. Likewise, there is no convincing evidence for the associations between leptin levels and cardiovascular diseases (CVD) risk factors.

Conclusions: This study did not provide evidence that leptin levels are associated with increased risk of stroke and its subtypes.