{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:08:46Z","timestamp":1782778126415,"version":"3.54.5"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,8,16]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We performed a 2\u2010sample inverse\u2010variance weighted Mendelian randomization analysis, multiple sensitivity analyses to assess pleiotropy and multivariate Mendelian randomization analyses to assess mediating\/confounding factors. European\u2010ancestry genomic summary data (\n              <jats:italic>P<\/jats:italic>\n              &lt;5\u00d710\n              <jats:sup>\u22128<\/jats:sup>\n              ) for type 2 diabetes, lipid\u2010fractions, smoking, alcohol and coffee consumption, physical activity, sleep, and education level were selected. Genetic associations with PAD were extracted from the Million\u2010Veteran\u2010Program genome\u2010wide association studies (cases=31\u2009307, controls=211\u2009753, 72% European\u2010ancestry) and the GoLEAD\u2010SUMMIT genome\u2010wide association studies (11 independent genome\u2010wide association studies, European\u2010ancestry, cases=12\u2009086, controls=449\u2009548). Associations were categorized as robust (Bonferroni\u2010significant (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.00294), consistent over PAD\u2010cohorts\/sensitivity analyses), suggestive (\n              <jats:italic>P<\/jats:italic>\n              value: 0.00294\u20130.05, associations in 1 PAD\u2010cohort\/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\u2010density lipoprotein cholesterol, triglyceride\u2010levels, alcohol consumption, and inverse associations for high\u2010density lipoprotein cholesterol, and increased sleep duration were found. No associations were found for physical activity and coffee consumption. However, effects fully attenuated for low\u2010density lipoprotein cholesterol and triglycerides after correcting for apoB, and for insomnia after correcting for body mass index and lipid\u2010fractions. Nonsignificant attenuation by potential mediators was observed for education level and type 2 diabetes.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Detrimental effects of smoking and type 2 diabetes, but not of low\u2010density 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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.025644","type":"journal-article","created":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T09:16:43Z","timestamp":1659691003000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Causal Association of Cardiovascular Risk Factors and Lifestyle Behaviors With Peripheral Artery Disease: A Mendelian Randomization Approach"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3656-7872","authenticated-orcid":false,"given":"Anna G.","family":"Hoek","sequence":"first","affiliation":[{"name":"Amsterdam UMC location Vrije Universiteit Amsterdam Epidemiology and Data Science Amsterdam The Netherlands"},{"name":"Amsterdam Cardiovascular Sciences Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0756-2730","authenticated-orcid":false,"given":"Sabine","family":"van Oort","sequence":"additional","affiliation":[{"name":"Amsterdam UMC location Vrije Universiteit Amsterdam Epidemiology and Data Science Amsterdam The Netherlands"},{"name":"Amsterdam UMC location Vrije Universiteit Amsterdam General Practice Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5907-7219","authenticated-orcid":false,"given":"Petra J. 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