Effects of maternal and paternal smoking on offspring cardiometabolic risk factors in adulthood: a multi-method intergenerational Mendelian randomization study

Investigating the potential causal relationship between parity and long-term maternal cardiometabolic health outcomes using Mendelian randomization

Findings indicate a possible causal relationship between NEB and long-term cardiometabolic health, although causal effects are likely to be small.

Association of maternal cardiovascular health in early-to-mid pregnancy with offspring cardiovascular phenotypes in early childhood: a prospective birth cohort study.

Intergenerational and life-course links between a cardiovascular health-related methylation score and early vascular changes

An LE8-derived DNAm score was associated with lower cIMT across the life course and, to a lesser extent, across generations, suggesting that blood DNAm reflects cumulative cardiovascular health and vascular burden and may complement conventional cardiovascular risk assessment.

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

BACKGROUND In this two-sample, two-step Mendelian randomization (MR) study, we aimed to elucidate the causal associations between sarcopenia-related characteristics and heart failure (HF) risk, and to identify the factors mediating these associations, with a particular focus on the mediating roles of obesity and sedentary habits. METHODS Genetic instruments for appendicular lean mass (ALM), hand grip strength (HGS), walking pace (WP) and potential mediators were extracted from genome-wide association studies (GWASs). Inverse-variance weighting (IVW) was used as the primary analytical method, supplemented by MR-Egger regression, weighted median, and weighted mode analyses. Sensitivity analyses including Cochran's Q test and MR-Egger intercept method were performed to assess heterogeneity and pleiotropy. Bidirectional MR was conducted to exclude reverse causation. RESULTS IVW revealed that a faster genetically predicted walking pace (WP) was associated with lower HF risk (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.33-0.60, P = 5.806 × 10-7). The mediation analysis indicated that body mass index accounted for 32% of this effect, while time spent watching television accounted for 14%. Elevated appendicular lean mass showed a slight but significant positive association with HF risk (OR 1.06, 95% CI 1.03-1.09, P = 5.437 × 10-4). However, multivariable MR adjusting for BMI completely attenuated this association (P = 0.693), suggesting ALM reflects overall body composition rather than isolated muscle mass. No significant associations were found between HGS and HF. Bidirectional MR showed no robust reverse effects. CONCLUSIONS These findings suggest that genetically predicted increased WP exerts beneficial effects against HF, partially mediated by obesity and sedentary habits. Targeting weight management and anti-sedentary interventions may mitigate HF risk in individuals with sarcopenia-related characteristics.

Causal effects of diabetes and alcohol intake on Dupuytren's disease: a two-sample Mendelian randomization study in UK Biobank and FinnGen.

Background Dupuytren's disease (DD) is associated with metabolic and lifestyle traits. However, these associations remain uncertain because exposures frequently cluster, and conventional studies are vulnerable to residual confounding and reverse causation. Methods A two-sample Mendelian randomization (MR) analysis using genetic instruments for diabetes, obesity-related, smoking, and alcohol-related traits from genome-wide association studies of large European ancestry was conducted. Summary statistics of DD were obtained from UK Biobank and FinnGen and combined using meta-analysis. Multiplicative random-effects inverse variance weighted MR was used as the primary method, with complementary sensitivity analyses to test robustness. Results Genetic liability for diabetes was associated with a higher risk of DD (meta-analyzed odds ratio [OR], 1.0157; 95% confidence interval [CI], 1.0070-1.0245; P<0.001). Genetically predicted alcohol intake was also positively associated with DD (alcohol intake OR, 1.0150; 95% CI, 1.0087-1.0212; P<0.001; drinks per week OR, 1.0062; 95% CI, 1.0015-1.0110; P=0.0103). However, we found no convincing evidence that obesity traits or smoking intensity had causal effects on DD. Sensitivity analyses were directionally consistent, the instruments were adequately strong, and there was no substantial evidence of horizontal pleiotropy for the main associations. Although the observed effect sizes were modest, consistent with the multifactorial nature of DD, supporting directional risk associations rather than large individual-level effects. Conclusion 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. These findings suggest that better glycemic management and lower alcohol exposure may help reduce the risk of DD.

Acute maternal stress in pregnancy and cardiovascular risk factors in adolescent offspring: a birth-cohort study

Abstract Background Cardiometabolic risk factors are major contributors to poor health outcomes and premature mortality. While the effect of prenatal exposure to stress on cardiometabolic outcomes has been examined, the findings remain inconsistent across studies, and even more so with regard to the timing of exposure. In the present study, we aimed to explore the association of short-term prenatal exposure to the acute stress of the 1967 Six-Day War with cardiovascular and anthropometric risk factors in adolescent offspring. Methods Using a population-based birth cohort, we examined data from 61 237 offspring born in Jerusalem during 1964–76, linked to their military-draft records at age 17 years. These provided information on those exposed to acute prenatal stress and the timing of exposure within the pregnancy (N = 2471) as well as on height, weight, heart rate (HR), and blood pressure (BP) in adolescence. Linear regression models estimated the associations between prenatal stress and measurements at age 17 years, controlling for potential confounders. Results Prenatal exposure to acute stress was associated with increased systolic blood pressure (SBP) and diastolic blood pressure (DBP) [SBP: B = 1.85, 95% confidence interval (CI): 1.15, 2.56; DBP: B = 1.89, 95% CI: 1.40, 2.38] and a decreased HR (B = –1.39, CI: –1.88, –0.91) but not with anthropometric outcomes. Furthermore, gestational age at exposure modified these associations: the associations with DBP and mean arterial pressure tended to increase and with HR to decrease the later the exposure occurred during the pregnancy. Conclusion Findings suggest that acute maternal stress during pregnancy is associated with cardiovascular risk factors in offspring in adolescence and is modulated by the timing of the exposure.