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Genetic predisposition to Parkinson's disease and risk of cardio and cerebrovascular disease: a Mendelian randomization study
Observational studies suggest that Parkinson's disease (PD) is related with the risk of cardio and cerebrovascular disease. However, the causality is not yet fully established. Therefore, we employed Mendelian randomization to assess whether PD is related to risk of ischemic stroke (IS), IS sub...
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Published in: | Parkinsonism & related disorders 2022-01, Vol.94, p.49-53 |
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description | Observational studies suggest that Parkinson's disease (PD) is related with the risk of cardio and cerebrovascular disease. However, the causality is not yet fully established. Therefore, we employed Mendelian randomization to assess whether PD is related to risk of ischemic stroke (IS), IS subtypes, coronary artery disease (CAD) and myocardial infarction (MI).
Eighty-eight and eleven single nucleotide polymorphisms associated with PD at the genome-wide significance level, were used as instrumental variables for PD in European and East Asian population respectively. Using a 2-sample MR, we examined associations with IS, IS related subtypes, CAD and MI in European population. We also assessed the causal association of PD with IS and CAD in East Asian population. The primary MR analyses were performed by using the random-effects inverse variance weighted approach.
In European population, genetic predisposition to PD was related to higher risk of IS (odds ratio [OR], 1.03 per doubling in odds of PD; 95% confidence interval [CI], 1.01–1.05; P = 0.002) and cardioembolic stroke (OR, 1.08 per doubling in odds of PD; 95% CI, 1.04–1.12; P = 1.29 × 10−4), but not large artery stroke, small vessel stroke, CAD and MI. In East Asian population, we found no evidence of causal effect of PD on the risk of IS and CAD.
This study found that genetic predisposition to PD is related to higher risk of IS and cardioembolic stroke in European population.
•This study showed that genetic predisposition to PD is associated with higher risk of IS and CES in European population.•In East Asian population, we found no evidence of causal effect of PD on the risk of IS and CAD. |
doi_str_mv | 10.1016/j.parkreldis.2021.11.021 |
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Eighty-eight and eleven single nucleotide polymorphisms associated with PD at the genome-wide significance level, were used as instrumental variables for PD in European and East Asian population respectively. Using a 2-sample MR, we examined associations with IS, IS related subtypes, CAD and MI in European population. We also assessed the causal association of PD with IS and CAD in East Asian population. The primary MR analyses were performed by using the random-effects inverse variance weighted approach.
In European population, genetic predisposition to PD was related to higher risk of IS (odds ratio [OR], 1.03 per doubling in odds of PD; 95% confidence interval [CI], 1.01–1.05; P = 0.002) and cardioembolic stroke (OR, 1.08 per doubling in odds of PD; 95% CI, 1.04–1.12; P = 1.29 × 10−4), but not large artery stroke, small vessel stroke, CAD and MI. In East Asian population, we found no evidence of causal effect of PD on the risk of IS and CAD.
This study found that genetic predisposition to PD is related to higher risk of IS and cardioembolic stroke in European population.
•This study showed that genetic predisposition to PD is associated with higher risk of IS and CES in European population.•In East Asian population, we found no evidence of causal effect of PD on the risk of IS and CAD.</description><identifier>ISSN: 1353-8020</identifier><identifier>EISSN: 1873-5126</identifier><identifier>DOI: 10.1016/j.parkreldis.2021.11.021</identifier><identifier>PMID: 34883359</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Coronary artery disease ; Coronary Artery Disease - epidemiology ; Coronary Artery Disease - genetics ; Embolic Stroke ; Genetic Predisposition to Disease - genetics ; Genome-Wide Association Study ; Humans ; Mendelian randomization ; Mendelian Randomization Analysis ; Myocardial infarction ; Parkinson Disease - epidemiology ; Parkinson Disease - genetics ; Parkinson's disease ; Polymorphism, Single Nucleotide - genetics ; Risk Factors ; Stroke ; Stroke - etiology ; Stroke - genetics</subject><ispartof>Parkinsonism & related disorders, 2022-01, Vol.94, p.49-53</ispartof><rights>2021</rights><rights>Copyright © 2021. Published by Elsevier Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c374t-b9f132da67b1cde3378d699c83fbbef93227f67c5098d566e00eca21e11235ee3</citedby><cites>FETCH-LOGICAL-c374t-b9f132da67b1cde3378d699c83fbbef93227f67c5098d566e00eca21e11235ee3</cites><orcidid>0000-0001-9091-7581</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34883359$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Mengmeng</creatorcontrib><creatorcontrib>Zhang, Zhizhong</creatorcontrib><creatorcontrib>Liu, Dandan</creatorcontrib><creatorcontrib>Ji, Lei</creatorcontrib><creatorcontrib>Huang, Shuangjiao</creatorcontrib><creatorcontrib>Cao, Liping</creatorcontrib><creatorcontrib>Wei, Ning</creatorcontrib><creatorcontrib>Ye, Dan</creatorcontrib><creatorcontrib>Ma, Yazhou</creatorcontrib><creatorcontrib>Lian, Xuegan</creatorcontrib><title>Genetic predisposition to Parkinson's disease and risk of cardio and cerebrovascular disease: a Mendelian randomization study</title><title>Parkinsonism & related disorders</title><addtitle>Parkinsonism Relat Disord</addtitle><description>Observational studies suggest that Parkinson's disease (PD) is related with the risk of cardio and cerebrovascular disease. However, the causality is not yet fully established. Therefore, we employed Mendelian randomization to assess whether PD is related to risk of ischemic stroke (IS), IS subtypes, coronary artery disease (CAD) and myocardial infarction (MI).
Eighty-eight and eleven single nucleotide polymorphisms associated with PD at the genome-wide significance level, were used as instrumental variables for PD in European and East Asian population respectively. Using a 2-sample MR, we examined associations with IS, IS related subtypes, CAD and MI in European population. We also assessed the causal association of PD with IS and CAD in East Asian population. The primary MR analyses were performed by using the random-effects inverse variance weighted approach.
In European population, genetic predisposition to PD was related to higher risk of IS (odds ratio [OR], 1.03 per doubling in odds of PD; 95% confidence interval [CI], 1.01–1.05; P = 0.002) and cardioembolic stroke (OR, 1.08 per doubling in odds of PD; 95% CI, 1.04–1.12; P = 1.29 × 10−4), but not large artery stroke, small vessel stroke, CAD and MI. In East Asian population, we found no evidence of causal effect of PD on the risk of IS and CAD.
This study found that genetic predisposition to PD is related to higher risk of IS and cardioembolic stroke in European population.
•This study showed that genetic predisposition to PD is associated with higher risk of IS and CES in European population.•In East Asian population, we found no evidence of causal effect of PD on the risk of IS and CAD.</description><subject>Coronary artery disease</subject><subject>Coronary Artery Disease - epidemiology</subject><subject>Coronary Artery Disease - genetics</subject><subject>Embolic Stroke</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genome-Wide Association Study</subject><subject>Humans</subject><subject>Mendelian randomization</subject><subject>Mendelian Randomization Analysis</subject><subject>Myocardial infarction</subject><subject>Parkinson Disease - epidemiology</subject><subject>Parkinson Disease - genetics</subject><subject>Parkinson's disease</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Risk Factors</subject><subject>Stroke</subject><subject>Stroke - etiology</subject><subject>Stroke - genetics</subject><issn>1353-8020</issn><issn>1873-5126</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNqFkM1O3DAURq2qqNBpX6Hyjm6S-oc4Drt2BBQJRBft2nLsG8lDxg6-CRJIvDuGAbpk9Vn2ufeTDyGUs5ozrn5s6snm6wyjD1gLJnjNeV3iAzngupVVw4X6WM6ykZVmgu2Tz4gbxljbMPmJ7MsjraVsugPycAYR5uDolKEsmxKGOaRI50T_lIoQMcVDpOUJLAK10dMc8JqmgTqbfUjPVw4y9DndWnTLaPMrfkwtvYToYQw20lzItA339rkA58XffSF7gx0Rvr7kivw7Pfm7_l1dXJ2dr39eVE62R3PVdwOXwlvV9tx5kLLVXnWd03Loexg6KUQ7qNY1rNO-UQoYA2cFB86FbADkinzf7Z1yulkAZ7MN6GAcbYS0oBGK6Ua2qlhZEb1DXU6IGQYz5bC1-c5wZp7km435L988yTecmxJl9NtLy9Jvwb8NvtouwK8dAOWvtwGyQRcgumI-g5uNT-H9lkfDYZ3L</recordid><startdate>202201</startdate><enddate>202201</enddate><creator>Wang, Mengmeng</creator><creator>Zhang, Zhizhong</creator><creator>Liu, Dandan</creator><creator>Ji, Lei</creator><creator>Huang, Shuangjiao</creator><creator>Cao, Liping</creator><creator>Wei, Ning</creator><creator>Ye, Dan</creator><creator>Ma, Yazhou</creator><creator>Lian, Xuegan</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9091-7581</orcidid></search><sort><creationdate>202201</creationdate><title>Genetic predisposition to Parkinson's disease and risk of cardio and cerebrovascular disease: a Mendelian randomization study</title><author>Wang, Mengmeng ; Zhang, Zhizhong ; Liu, Dandan ; Ji, Lei ; Huang, Shuangjiao ; Cao, Liping ; Wei, Ning ; Ye, Dan ; Ma, Yazhou ; Lian, Xuegan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c374t-b9f132da67b1cde3378d699c83fbbef93227f67c5098d566e00eca21e11235ee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Coronary artery disease</topic><topic>Coronary Artery Disease - epidemiology</topic><topic>Coronary Artery Disease - genetics</topic><topic>Embolic Stroke</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genome-Wide Association Study</topic><topic>Humans</topic><topic>Mendelian randomization</topic><topic>Mendelian Randomization Analysis</topic><topic>Myocardial infarction</topic><topic>Parkinson Disease - epidemiology</topic><topic>Parkinson Disease - genetics</topic><topic>Parkinson's disease</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Risk Factors</topic><topic>Stroke</topic><topic>Stroke - etiology</topic><topic>Stroke - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Mengmeng</creatorcontrib><creatorcontrib>Zhang, Zhizhong</creatorcontrib><creatorcontrib>Liu, Dandan</creatorcontrib><creatorcontrib>Ji, Lei</creatorcontrib><creatorcontrib>Huang, Shuangjiao</creatorcontrib><creatorcontrib>Cao, Liping</creatorcontrib><creatorcontrib>Wei, Ning</creatorcontrib><creatorcontrib>Ye, Dan</creatorcontrib><creatorcontrib>Ma, Yazhou</creatorcontrib><creatorcontrib>Lian, Xuegan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Parkinsonism & related disorders</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Mengmeng</au><au>Zhang, Zhizhong</au><au>Liu, Dandan</au><au>Ji, Lei</au><au>Huang, Shuangjiao</au><au>Cao, Liping</au><au>Wei, Ning</au><au>Ye, Dan</au><au>Ma, Yazhou</au><au>Lian, Xuegan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic predisposition to Parkinson's disease and risk of cardio and cerebrovascular disease: a Mendelian randomization study</atitle><jtitle>Parkinsonism & related disorders</jtitle><addtitle>Parkinsonism Relat Disord</addtitle><date>2022-01</date><risdate>2022</risdate><volume>94</volume><spage>49</spage><epage>53</epage><pages>49-53</pages><issn>1353-8020</issn><eissn>1873-5126</eissn><abstract>Observational studies suggest that Parkinson's disease (PD) is related with the risk of cardio and cerebrovascular disease. However, the causality is not yet fully established. Therefore, we employed Mendelian randomization to assess whether PD is related to risk of ischemic stroke (IS), IS subtypes, coronary artery disease (CAD) and myocardial infarction (MI).
Eighty-eight and eleven single nucleotide polymorphisms associated with PD at the genome-wide significance level, were used as instrumental variables for PD in European and East Asian population respectively. Using a 2-sample MR, we examined associations with IS, IS related subtypes, CAD and MI in European population. We also assessed the causal association of PD with IS and CAD in East Asian population. The primary MR analyses were performed by using the random-effects inverse variance weighted approach.
In European population, genetic predisposition to PD was related to higher risk of IS (odds ratio [OR], 1.03 per doubling in odds of PD; 95% confidence interval [CI], 1.01–1.05; P = 0.002) and cardioembolic stroke (OR, 1.08 per doubling in odds of PD; 95% CI, 1.04–1.12; P = 1.29 × 10−4), but not large artery stroke, small vessel stroke, CAD and MI. In East Asian population, we found no evidence of causal effect of PD on the risk of IS and CAD.
This study found that genetic predisposition to PD is related to higher risk of IS and cardioembolic stroke in European population.
•This study showed that genetic predisposition to PD is associated with higher risk of IS and CES in European population.•In East Asian population, we found no evidence of causal effect of PD on the risk of IS and CAD.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>34883359</pmid><doi>10.1016/j.parkreldis.2021.11.021</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0001-9091-7581</orcidid></addata></record> |
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subjects | Coronary artery disease Coronary Artery Disease - epidemiology Coronary Artery Disease - genetics Embolic Stroke Genetic Predisposition to Disease - genetics Genome-Wide Association Study Humans Mendelian randomization Mendelian Randomization Analysis Myocardial infarction Parkinson Disease - epidemiology Parkinson Disease - genetics Parkinson's disease Polymorphism, Single Nucleotide - genetics Risk Factors Stroke Stroke - etiology Stroke - genetics |
title | Genetic predisposition to Parkinson's disease and risk of cardio and cerebrovascular disease: a Mendelian randomization study |
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