Findings indicate a possible causal relationship between NEB and long-term cardiometabolic health, although causal effects are likely to be small.
Abstract
Background: Multiple observational studies have reported associations between greater parity and increased CVD risk. Whether these associations reflect causal effects or are confounded by socioeconomic factors remains unclear. Methods: We investigated associations between number of children ever born (NEB) and 16 cardiometabolic traits in up to 172,122 females and 138,390 males in the UK Biobank, and an independent sample of 53,237 UK Biobank spousal pairs. We additionally conducted sex-stratified two-sample Mendelian randomization (MR) and applied a novel spousal MR framework, in which an individual's spouse's genotype was used as the instrumental variable to estimate the causal effect of NEB on cardiometabolic health outcomes, as an approach to minimize bias from horizontal pleiotropy. Results: NEB was associated with multiple cardiometabolic traits in the multivariable regression, even after adjustment for socioeconomic status, with differences in the strength of association observed between males and females. Traditional MR provided evidence that higher NEB causally increases type 2 diabetes risk in females, body mass index (BMI) in both sexes, female basal metabolic rate (BMR) and male body fat percentage but decreases female blood pressure. Spousal MR corroborated positive effects on female BMI and BMR and additionally suggested inverse causal effects on female HDL cholesterol and ApoA1 and male blood glucose. Conclusion: These findings indicate a possible causal relationship between NEB and long-term cardiometabolic health, although causal effects are likely to be small.
Little evidence that maternal smoking initiation affected WHR is found, and little evidence that maternal smoking heaviness affected the remaining cardiometabolic risk factors; paternal smoking showed no clear effect on any outcome.
G. Power, T. Bond, L. Bhatta et al.· BMC Medicine· 0 citations
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.
Yaping Zhang, Han Xu, Xinkai Qu et al.· The Cardiology· 0 citations
It is suggested that elevated triglyceride levels are significantly associated with increased prevalence of hypertension, highlighting the potential importance of lipid management in hypertension prevention.
Shangsong Liang, Xue-Qin Pan, Xiao-Feng Fan et al.· Cardiovascular Journal of Af...· 0 citations
This MR study supported diabetes liability and higher alcohol intake as causal risk factors for DD, whereas genetically proxied obesity and smoking traits showed no clear causal effects, suggesting that better glycemic management and lower alcohol exposure may help reduce the risk of DD.
Heng Tian, Ling Hong, Wenlai Guo et al.· Korean Journal of Family Med...· 0 citations
This study investigates the potential causal relationship between circulating ketone bodies, specifically beta-hydroxybutyrate (β-OHB), and the risk of myocardial infarction (MI), addressing limitations of confounding and reverse causation inherent in previous observational studies. We employed both univariable Mendelian randomization and multivariable Mendelian randomization (MVMR) analyses using publicly available genome-wide association study summary statistics. Genetic variants robustly associated with serum β-OHB levels (P < 5 × 10−8) served as instrumental variables. Primary analysis used the inverse-variance weighted method, supplemented by sensitivity analyses (MR-Egger, weighted median, weighted mode, MR-Lasso) and tests for pleiotropy/heterogeneity (Cochran’s Q, MR-Egger intercept, MR-Pleiotropy RESidual Sum and Outlier, leave-one-out). The MVMR model adjusted for key cardiometabolic confounders: type 2 diabetes, alcohol intake, body mass index, smoking, hypertension, and blood lipids. univariable Mendelian randomization analysis indicated a significant positive association: a one-unit increase in natural log-transformed β-OHB concentration was associated with higher MI risk (IVW odds ratio [OR] = 1.407, 95% confidence interval (CI): 1.1660–1.6980, P = .0003691). Sensitivity analyses (weighted median: OR = 1.260, 95% CI: 1.0022–1.585, P = .0478442; MR-Egger: directionally consistent) supported this finding. MVMR analysis adjusting for confounders yielded divergent results. While conventional IVW showed no significant independent association (OR = 0.9787, 95% CI: 0 0.7410–1.2928, P = .8797), the MR-Lasso method revealed a significant independent positive association between β-OHB and MI risk (OR = 1.2366, 95% CI: 1.0397–1.4707, P = .0163751). This Mendelian randomization study suggests that genetically predicted, chronically elevated levels of β-OHB may confer an increased risk of MI.
Abstract Introduction Female reproductive traits influence bone mineral density (BMD) and fracture risks through estrogen exposure. However, these causal relationships remain unclear due to confounding. Understanding these relationships is crucial for osteoporosis prevention strategies. This study aimed to investigate the causal impact of age at natural menopause (ANM) and age at menarche (AAM) on BMD and osteoporosis risk, and to explore gene-exercise interactions influencing bone health in East Asian women. Methods We conducted two-sample Mendelian randomization (MR) using 15 genetic variants for AAM and 36 variants for ANM in 51,049 women from the Taiwan Biobank, split into discovery (n = 25,549) and validation (n = 25,500) cohorts. Outcomes were BMD Z scores, T scores, and clinical osteoporosis. We performed univariable and multivariable MR, followed by regression analyses, focusing on exercise effects on BMD and genetic predisposition scores for AAM and ANM. Results In multivariable MR, genetically determined later ANM was associated with higher BMD Z scores (β = 0.045, 95% confidence interval [0.021, 0.069]), higher T scores (β = 0.046, [0.020, 0.072]), and lower osteoporosis risk (β = −0.106, [−0.154, −0.058]). No consistent causal effect was observed for AAM due to genetic pleiotropy. ANM polygenic risk score and regular exercise were independently associated with improved BMD Z- and T scores and reduced risk of osteoporosis. Specific gene-exercise interactions were identified in which the AAM polygenic risk score interacted significantly with gymnastics, while the ANM polygenic risk score interacted with lower-limb exercise and swimming. Conclusion Late ANM provides causal protection against osteoporosis in East Asian women, while the effects of AAM remain insignificant. Exercise benefits bone health with activity-specific genetic interactions. These findings support personalized osteoporosis prevention strategies incorporating both genetic risk assessment and targeted exercise recommendations, particularly for women with early menopause predisposition.
Bo-Kai Chen, J. Cambia, Chien-An Shih et al.· Lifestyle Genomics· 0 citations
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