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Causal Association of Cardiovascular Risk Factors and Lifestyle Behaviors With Peripheral Artery Disease: A Mendelian Randomization Approach.
- Source :
-
Journal of the American Heart Association [J Am Heart Assoc] 2022 Aug 16; Vol. 11 (16), pp. e025644. Date of Electronic Publication: 2022 Aug 05. - Publication Year :
- 2022
-
Abstract
- 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 <superscript>-8</superscript> ) 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.
- Subjects :
- Cholesterol, HDL
Cholesterol, LDL
Coffee
Genome-Wide Association Study
Heart Disease Risk Factors
Humans
Life Style
Mendelian Randomization Analysis methods
Polymorphism, Single Nucleotide
Risk Factors
Smoking adverse effects
Triglycerides
Cardiovascular Diseases genetics
Diabetes Mellitus, Type 2 diagnosis
Diabetes Mellitus, Type 2 epidemiology
Diabetes Mellitus, Type 2 genetics
Peripheral Arterial Disease diagnosis
Peripheral Arterial Disease epidemiology
Peripheral Arterial Disease genetics
Sleep Initiation and Maintenance Disorders
Subjects
Details
- Language :
- English
- ISSN :
- 2047-9980
- Volume :
- 11
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Journal of the American Heart Association
- Publication Type :
- Academic Journal
- Accession number :
- 35929454
- Full Text :
- https://doi.org/10.1161/JAHA.122.025644