Dataset Information

Association of cardiovascular risk factors and lifestyle behaviors with aortic aneurysm: A Mendelian randomization study.

ABSTRACT: Objective: To examine the causality between hypertension, diabetes, other cardiovascular risk factors, lifestyle behaviors, and the aortic aneurysm among patients of European ancestry. Methods: We performed two-sample Mendelian randomization (MR) analysis to investigate the causality of 12 modifiable risk factors with aortic aneurysm, including hypertension, body mass index (BMI), waist-hip ratio (WHR), diabetes, tobacco smoking, alcohol and coffee consumption, physical activity, and sleep duration. Genome-wide significant genetic instruments (p < 5 × 10^-8) for risk factors were extracted from European-descent genome-wide association studies, whereas aortic aneurysm genetic instruments were selected from the UK Biobank and FinnGen cohort. The inverse-variance weighted MR was used as the main analysis, and MR-Egger (MRE), weighted median MR, MR pleiotropy residual sum and outlier, and Phenoscanner searching were performed as sensitivity analyses. Furthermore, we calculated MRE intercept to detect pleiotropy and Cochran's Q statistics to assess heterogeneity and conducted bidirectional MR and MR Steiger tests to exclude the possibility of reverse causality. Results: We observed significantly higher risks for the aortic aneurysm in hypertension [pooled OR: 4.30 (95% CI 2.84-6.52)], BMI [OR: 1.58 (95% CI 1.37-1.81)], WHR [OR: 1.51 (95% CI 1.21-1.88)], WHR adjusted for BMI (WHRadjBMI) [OR: 1.35 (95% CI 1.12-1.63)], age of smoking initiation [OR: 1.63 (95% CI 1.18-2.26)], and tobacco use (initiation, cessation, and heaviness) [OR: 2.88 (95% CI 1.85-2.26)]. In sensitivity analysis, the causal effects of hypertension, BMI, WHRadjBMI, and tobacco use (initiation, cessation, and heaviness) remained robust. Conclusion: There was a positive causal relationship between hypertension, BMI, WHR, and WHRadjBMI and aortic aneurysm.

SUBMITTER: Zhou J

PROVIDER: S-EPMC9393757 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of cardiovascular risk factors and lifestyle behaviors with aortic aneurysm: A Mendelian randomization study.

Zhou Jiawei J Lin Jianfeng J Zheng Yuehong Y

Frontiers in genetics 20220808

<b>Objective:</b> To examine the causality between hypertension, diabetes, other cardiovascular risk factors, lifestyle behaviors, and the aortic aneurysm among patients of European ancestry. <b>Methods:</b> We performed two-sample Mendelian randomization (MR) analysis to investigate the causality of 12 modifiable risk factors with aortic aneurysm, including hypertension, body mass index (BMI), waist-hip ratio (WHR), diabetes, tobacco smoking, alcohol and coffee consumption, physical activity, a ...[more]

PMID: 36003339

Similar Datasets

Project description:Background We investigated the causal associations between the genetic liability to cardiovascular and lifestyle risk factors and peripheral artery disease (PAD), using a Mendelian randomization approach. Methods and Results We performed a 2-sample inverse-variance weighted Mendelian randomization analysis, multiple sensitivity analyses to assess pleiotropy and multivariate Mendelian randomization analyses to assess mediating/confounding factors. European-ancestry genomic summary data (P<5×10-8) for type 2 diabetes, lipid-fractions, smoking, alcohol and coffee consumption, physical activity, sleep, and education level were selected. Genetic associations with PAD were extracted from the Million-Veteran-Program genome-wide association studies (cases=31 307, controls=211 753, 72% European-ancestry) and the GoLEAD-SUMMIT genome-wide association studies (11 independent genome-wide association studies, European-ancestry, cases=12 086, controls=449 548). Associations were categorized as robust (Bonferroni-significant (P<0.00294), consistent over PAD-cohorts/sensitivity analyses), suggestive (P value: 0.00294-0.05, associations in 1 PAD-cohort/inconsistent sensitivity analyses) or not present. Robust evidence for genetic liability to type 2 diabetes, smoking, insomnia, and inverse associations for higher education level with PAD were found. Suggestive evidence for the genetic liability to higher low-density lipoprotein cholesterol, triglyceride-levels, alcohol consumption, and inverse associations for high-density lipoprotein cholesterol, and increased sleep duration were found. No associations were found for physical activity and coffee consumption. However, effects fully attenuated for low-density lipoprotein cholesterol and triglycerides after correcting for apoB, and for insomnia after correcting for body mass index and lipid-fractions. Nonsignificant attenuation by potential mediators was observed for education level and type 2 diabetes. Conclusions Detrimental effects of smoking and type 2 diabetes, but not of low-density lipoprotein cholesterol and triglycerides, on PAD were confirmed. Lower education level and insomnia were identified as novel risk factors for PAD; however, complete mediation for insomnia and incomplete mediation for education level by downstream risk factors was observed.

Project description:BACKGROUND: Vitamin D deficiency is associated with increased cardiovascular disease risk in observational studies. Whether these associations are causal is not clear. Loss-of-function mutations in the filaggrin gene result in up to 10% higher serum vitamin D concentrations, supposedly due to a decreased UV-protection of the keratinocytes. We used a Mendelian randomization approach to estimate the causal effect of vitamin D status on serum lipids, blood pressure, body mass index, waist circumference, and the metabolic syndrome. METHODS: Three population based studies were included, Monica10 (2,656 individuals aged 40-71 years), Inter99 (6,784 individuals aged 30-60 years), and Health2006 (3,471 individuals aged 18-69 years) conducted in 1993-94, 1999-2001, and 2006-2008, respectively. Participants were genotyped for the two most common filaggrin gene mutations in European descendants R501X and 2282del4, in all three studies and further for the R2447X mutation in the Inter99 and Health2006 studies. Filaggrin genotype was used as instrumental variable for vitamin D status. Baseline measurements of serum 25-hydroxyvitamin D were performed in all three studies. RESULTS: Instrumental variable analyses showed a 23.8% (95% confidence interval, CI 3.0, 48.6) higher HDL cholesterol level and a 30.5% (95% CI: 0.8, 51.3) lower serum level of triglycerides per doubling of vitamin D. These associations were, however, not statistically significant when applying the Bonferroni adjusted significance level. The remaining lipids showed non-significant changes in a favorable direction. Doubling of vitamin D gave a non-significantly lower odds ratio = 0.26 (95% CI: 0.06, 1.17) of the metabolic syndrome. There were no statistically significant causal effects of vitamin D status on blood pressure, body mass index, or waist circumference. CONCLUSION: Our results support a causal effect of higher vitamin D status on a more favorable lipid profile, although more studies in other populations are needed to confirm our results.

Dataset Information

Association of cardiovascular risk factors and lifestyle behaviors with aortic aneurysm: A Mendelian randomization study.

Publications

Association of cardiovascular risk factors and lifestyle behaviors with aortic aneurysm: A Mendelian randomization study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets