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Causal Association of Cardiovascular Risk Factors and Lifestyle Behaviors With Peripheral Artery Disease: A Mendelian Randomization Approach
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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496309/ https://www.ncbi.nlm.nih.gov/pubmed/35929454 http://dx.doi.org/10.1161/JAHA.122.025644 |
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author | Hoek, Anna G. van Oort, Sabine Elders, Petra J. M. Beulens, Joline W. J. |
author_facet | Hoek, Anna G. van Oort, Sabine Elders, Petra J. M. Beulens, Joline W. J. |
author_sort | Hoek, Anna G. |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-9496309 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94963092022-09-30 Causal Association of Cardiovascular Risk Factors and Lifestyle Behaviors With Peripheral Artery Disease: A Mendelian Randomization Approach Hoek, Anna G. van Oort, Sabine Elders, Petra J. M. Beulens, Joline W. J. J Am Heart Assoc Original Research 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. John Wiley and Sons Inc. 2022-08-05 /pmc/articles/PMC9496309/ /pubmed/35929454 http://dx.doi.org/10.1161/JAHA.122.025644 Text en © 2022 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Research Hoek, Anna G. van Oort, Sabine Elders, Petra J. M. Beulens, Joline W. J. Causal Association of Cardiovascular Risk Factors and Lifestyle Behaviors With Peripheral Artery Disease: A Mendelian Randomization Approach |
title | Causal Association of Cardiovascular Risk Factors and Lifestyle Behaviors With Peripheral Artery Disease: A Mendelian Randomization Approach |
title_full | Causal Association of Cardiovascular Risk Factors and Lifestyle Behaviors With Peripheral Artery Disease: A Mendelian Randomization Approach |
title_fullStr | Causal Association of Cardiovascular Risk Factors and Lifestyle Behaviors With Peripheral Artery Disease: A Mendelian Randomization Approach |
title_full_unstemmed | Causal Association of Cardiovascular Risk Factors and Lifestyle Behaviors With Peripheral Artery Disease: A Mendelian Randomization Approach |
title_short | Causal Association of Cardiovascular Risk Factors and Lifestyle Behaviors With Peripheral Artery Disease: A Mendelian Randomization Approach |
title_sort | causal association of cardiovascular risk factors and lifestyle behaviors with peripheral artery disease: a mendelian randomization approach |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496309/ https://www.ncbi.nlm.nih.gov/pubmed/35929454 http://dx.doi.org/10.1161/JAHA.122.025644 |
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