Triglycerides and Hypertension in a Korean Population: An Individual-Level Mendelian Randomization Analysis

Background: Although elevated triglyceride (TG) levels are consistently associated with hypertension in observational studies, whether TGs have a causal effect on hypertension remains uncertain, and evidence in East Asian populations is limited. Methods: We analyzed 2159 Korean adults (20-86 years) whose individual-level genetic and phenotypic data were obtained from a cross-sectional health check cohort. Candidate TG-associated genetic variants were identified using genome-wide association analysis and evaluated as instrumental variables (IVs). An individual-level, two-stage IV Mendelian randomization (MR) framework was applied to assess the potential effect of TGs on hypertension, alongside conventional observational analyses using logistic regression. Results: Three candidate TG-associated single-nucleotide polymorphisms (SNPs)-rs78115082 (TRPC7), rs117867615 (TTLL1), and rs34463296 (LINC03019)-were identified and combined to construct a weighted genetic risk score (GRS). Although all the instruments met the conventional strength criteria (F statistics > 10), they explained only a modest proportion of the variance in TG levels (partial R², 0.008-0.020). Observational analyses showed a strong positive association between TG levels and hypertension (crude odds ratio [OR] = 2.12; 95% confidence interval [CI]: 1.76-2.54; adjusted OR = 1.43; 95% CI: 1.16-1.75). In contrast, MR estimates based on individual SNPs and the GRS were directionally positive but statistically nonsignificant, with wide CIs crossing the null, indicating limited precision. Conclusions: In this Korean cohort, observational analyses demonstrated a robust association between TG levels and hypertension, whereas individual-level MR provided inconclusive genetic evidence for a causal effect under the available instruments. The difference between the observational and genetic estimates is compatible with the finding that TG levels reflect broader cardiometabolic dysregulation rather than acting as an isolated causal determinant of hypertension. These findings underscore the need for larger studies with stronger, externally derived instruments to refine the causal inference in East Asian populations.