Association and causality between triglycerides and hypertension: evidence from NHANES 2007-2018 and two-sample Mendelian randomisation analysis.

Depression as a mediator in the link between physical activity and cardiovascular disease: Insights from NHANES 2007–2018 and Mendelian randomization

The association between triglyceride-glucose index and all-cause mortality in postmenopausal women: A cohort study from NHANES

Elevated triglyceride–glucose (TyG) index has been linked to cardiovascular risk and metabolic disorders, but its relationship with all-cause mortality in postmenopausal women remains unclear. We aimed to investigate the association between baseline TyG index and all-cause mortality among postmenopausal women, and to determine whether a nonlinear (threshold) relationship exists. We conducted a prospective cohort study using data from the U.S. National Health and Nutrition Examination Survey 2001–2014. Participants were 3925 postmenopausal women (weighted mean age 63.1 years). Fasting subsample survey weights were applied, and the complex multistage sampling design (stratification and clustering) was fully accounted for in all analyses. TyG index was calculated from fasting triglyceride and glucose measurements. The main outcome was all-cause mortality. We used restricted cubic splines and design-based two-piecewise Cox proportional hazards regression to model nonlinear associations and identify a potential threshold. Over a median follow-up of approximately 9.9 years, 1088 deaths occurred (27.7% of participants). The association was nonlinear: the two-piecewise Cox analysis identified a significant threshold at TyG = 9.06 (95% confidence interval [CI] 8.92–9.26). Below the threshold, TyG index was not significantly associated with mortality (hazard ratio 0.88, 95% CI 0.69–1.11). Above this threshold, each 1-unit increase in TyG was associated with a 44% higher risk of all-cause mortality (hazard ratio 1.44, 95% CI 1.05–1.96, P = .020) after full adjustment for covariates. In this cohort of U.S. postmenopausal women, an elevated TyG index above 9.06 was associated with increased all-cause mortality. The relationship was nonlinear, with a risk threshold. This threshold should be considered exploratory and requires external validation before clinical use.

Mediating effects of body mass index on the association between obstructive sleep apnea and hypertension: a Mendelian randomization study

This study aims to evaluate the mediating effects of body mass index (BMI) on the association between obstructive sleep apnea (OSA) and hypertension using a two-sample multivariate Mendelian randomization (MR) study method. Summary statistics from publicly available genome-wide association studies were used for univariate and multivariate MR analyses to estimate the causal relationships and mediating effects of BMI. The inverse variance weighted (IVW) method was used as the main method for effect estimation, with additional methods including weighted median (WME), weighted mode (WM), MR-Egger regression, and the simple mode method (SM). Heterogeneity and pleiotropy in the study were assessed using the IVW method and pleiotropy residual and outlier analysis in Mendelian randomization (MR-PRESSO). The odds ratios (ORs) from univariate MR analyses regarding OSA and BMI on hypertension were 1.291 (95% CI: 1.111-1.500) and 1.981 (95% CI: 1.841-2.132), respectively. The multivariable MR analysis showed that the odds ratio for the association between OSA and hypertension was 1.051 (95% CI: 0.943-1.173). Further analysis indicated that BMI played a mediating role in the relationship between OSA and hypertension, with a mediation effect of 0.09 and a proportion of 34.6% (Sobel-test, P < .001). OSA is a risk factor of hypertension, and BMI has a mediating effect on the association.

Causal Associations and Potential Mediating Factors Between Sarcopenia-related Traits and Heart Failure Risk: A Mendelian Randomization Study.

It is suggested that genetically predicted increased WP exerts beneficial effects against HF, partially mediated by obesity and sedentary habits, and targeting weight management and anti-sedentary interventions may mitigate HF risk in individuals with sarcopenia-related characteristics.

Investigating the causal association between liver condition and melanoma: evidence from the National Health and Nutrition Examination Survey and Mendelian randomization.

This study aimed to investigate the association between liver condition and the risk of melanoma. We first conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2001 to 2004, involving 7144 participants (49 melanoma cases). The association was examined using multivariable logistic regression (three models), smooth curve fitting, and stratified analysis. To infer causality, a Mendelian randomization analysis was then performed using five algorithms, with sensitivity analyses and a Steiger test to validate the findings. In the NHANES analysis, liver condition was significantly associated with an increased risk of melanoma across all models [model 3: odds ratio (OR) = 4.31, 95% confidence interval (CI): 1.47-12.7]. The Mendelian randomization analysis using the inverse variance weighted method confirmed a positive causal relationship, identifying liver condition as a risk factor for melanoma (OR = 1.173, 95% CI: 1.051-1.310). Sensitivity analyses indicated no heterogeneity or horizontal pleiotropy, and the Steiger test supported the direction of causality. This study suggests a causal association between liver condition and melanoma, offering new insights for the prevention and treatment of melanoma.

Causal association between hip osteoarthritis and the risk of pancreatic cancer: A bidirectional two-sample Mendelian randomization study

The potential causal relationship between hip osteoarthritis (HOA) and pancreatic cancer (PC) is not well understood. To investigate this, our study utilized a two-sample Mendelian randomization (MR) method to examine a possible causal link between HOA and an increased risk of PC. Genome-wide association study summary data for both HOA and PC were sourced from the Integrative Epidemiology Unit OpenGWAS database (https://gwas.mrcieu.ac.uk/datasets/). The single-nucleotide polymorphisms associated with these conditions at a statistically significant level (P value <5 × 10−8) were identified as instrumental variables for subsequent analysis. We conducted bidirectional two-sample MR analyses employing inverse-variance weighting (IVW), weighted median, MR-Egger regression, and weighted mode methods. The robustness of the findings was assessed through sensitivity testing. The IVW analysis indicated that HOA elevated the risk of PC (odds ratio = 1.788; 95% confidence interval: 1.166–2.742; P = .008). Conversely, in the reverse MR analysis, the IVW analysis provided no evidence that PC increased the risk of HOA (odds ratio = 1.016; 95% confidence interval: 0.973–1.060; P = .475). In addition, the weighted mode, weighted median, and MR-Egger regression methods did not uncover a causal relationship. There was no heterogeneity or horizontal pleiotropy among the instrumental variables. The “leave-one-out” analysis revealed that no single-nucleotide polymorphism significantly influenced the overall results. Genetically predicted HOA is significantly associated with an increased risk of PC. However, we found no evidence that PC leads to an increased risk of HOA.