Genetic overlap between multiple sclerosis and several cardiovascular disease risk factors
Background: Epidemiological findings suggest a relationship between multiple sclerosis (MS) and cardiovascular disease (CVD) risk factors, although the nature of this relationship is not well understood. Objective: We used genome-wide association study (GWAS) data to identify shared genetic factors...
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| Veröffentlicht in: | Multiple sclerosis 2016-12, Vol.22 (14), p.1783-1793 |
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| container_title | Multiple sclerosis |
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| creator | Wang, Yunpeng Bos, Steffan D Harbo, Hanne F Thompson, Wesley K Schork, Andrew J Bettella, Francesco Witoelar, Aree Lie, Benedicte A Li, Wen McEvoy, Linda K Djurovic, Srdjan Desikan, Rahul S Dale, Anders M Andreassen, Ole A |
| description | Background:
Epidemiological findings suggest a relationship between multiple sclerosis (MS) and cardiovascular disease (CVD) risk factors, although the nature of this relationship is not well understood.
Objective:
We used genome-wide association study (GWAS) data to identify shared genetic factors (pleiotropy) between MS and CVD risk factors.
Methods:
Using summary statistics from a large, recent GWAS (total n > 250,000 individuals), we investigated overlap in single nucleotide polymorphisms (SNPs) associated with MS and a number of CVD risk factors including triglycerides (TG), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, body mass index, waist-to-hip ratio, type 2 diabetes, systolic blood pressure, and C-reactive protein level.
Results and conclusion:
Using conditional enrichment plots, we found 30-fold enrichment of MS SNPs for different levels of association with LDL and TG SNPs, with a corresponding reduction in conditional false discovery rate (FDR). We identified 133 pleiotropic loci outside the extended major histocompatibility complex with conditional FDR |
| doi_str_mv | 10.1177/1352458516635873 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5001937</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_1352458516635873</sage_id><sourcerecordid>1826653808</sourcerecordid><originalsourceid>FETCH-LOGICAL-c495t-44ebf7c54f96be491f596c150c9991aac51c61ef50f91f16a1367c870ff946d33</originalsourceid><addsrcrecordid>eNqNkc9rFTEQx4MotlbvnkrAi5etyebX5lKQUluh4EUvXkJedlLT5m1eM7uv-N-b8mppC4KnCXw_853JfAl5z9kR58Z84kL1Ug2Kay3UYMQLss-lMR2zhr1s7yZ3d_oeeYN4xRgzRqjXZK_XtmfC6H3y8wwmmFOgZQs1-w1dwXwLMNH1kue0yUAxZKgFE1I_jRShcT7T4OuYytZjWLKvdEwIHoHWhNc0-jCXim_Jq-gzwrv7ekB-fDn9fnLeXXw7-3ry-aIL0qq5kxJW0QQlo9UrkJZHZXXgigVrLfc-KB40h6hYbBrXngttwmBYjFbqUYgDcrzz3SyrNYwBprlt6DY1rX397YpP7qkypV_usmydYoxbYZrBx3uDWm4WwNmtEwbI2U9QFnR8UIoNjEv7H2ivtRIDGxr64Rl6VZY6tUs0qoUk5SD7RrEdFdqNsUJ82Jszd5exe55xazl8_N-Hhr-hNqDbAegv4dHUfxn-AUZOr4Y</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1847744842</pqid></control><display><type>article</type><title>Genetic overlap between multiple sclerosis and several cardiovascular disease risk factors</title><source>MEDLINE</source><source>SAGE Complete</source><creator>Wang, Yunpeng ; Bos, Steffan D ; Harbo, Hanne F ; Thompson, Wesley K ; Schork, Andrew J ; Bettella, Francesco ; Witoelar, Aree ; Lie, Benedicte A ; Li, Wen ; McEvoy, Linda K ; Djurovic, Srdjan ; Desikan, Rahul S ; Dale, Anders M ; Andreassen, Ole A</creator><creatorcontrib>Wang, Yunpeng ; Bos, Steffan D ; Harbo, Hanne F ; Thompson, Wesley K ; Schork, Andrew J ; Bettella, Francesco ; Witoelar, Aree ; Lie, Benedicte A ; Li, Wen ; McEvoy, Linda K ; Djurovic, Srdjan ; Desikan, Rahul S ; Dale, Anders M ; Andreassen, Ole A</creatorcontrib><description>Background:
Epidemiological findings suggest a relationship between multiple sclerosis (MS) and cardiovascular disease (CVD) risk factors, although the nature of this relationship is not well understood.
Objective:
We used genome-wide association study (GWAS) data to identify shared genetic factors (pleiotropy) between MS and CVD risk factors.
Methods:
Using summary statistics from a large, recent GWAS (total n > 250,000 individuals), we investigated overlap in single nucleotide polymorphisms (SNPs) associated with MS and a number of CVD risk factors including triglycerides (TG), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, body mass index, waist-to-hip ratio, type 2 diabetes, systolic blood pressure, and C-reactive protein level.
Results and conclusion:
Using conditional enrichment plots, we found 30-fold enrichment of MS SNPs for different levels of association with LDL and TG SNPs, with a corresponding reduction in conditional false discovery rate (FDR). We identified 133 pleiotropic loci outside the extended major histocompatibility complex with conditional FDR < 0.01, of which 65 are novel. These pleiotropic loci were located on 21 different chromosomes. Our findings point to overlapping pathobiology between clinically diagnosed MS and cardiovascular risk factors and identify novel common variants associated with increased MS risk.</description><identifier>ISSN: 1352-4585</identifier><identifier>EISSN: 1477-0970</identifier><identifier>DOI: 10.1177/1352458516635873</identifier><identifier>PMID: 26920376</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Cardiovascular disease ; Cardiovascular Diseases - blood ; Cardiovascular Diseases - epidemiology ; Cardiovascular Diseases - genetics ; Cardiovascular Diseases - physiopathology ; Genetic Loci ; Genetic Pleiotropy ; Genome-Wide Association Study ; Health risk assessment ; Humans ; Low density lipoprotein ; Multiple sclerosis ; Multiple Sclerosis - genetics ; Polymorphism, Single Nucleotide ; Risk Factors</subject><ispartof>Multiple sclerosis, 2016-12, Vol.22 (14), p.1783-1793</ispartof><rights>The Author(s), 2016</rights><rights>The Author(s), 2016.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c495t-44ebf7c54f96be491f596c150c9991aac51c61ef50f91f16a1367c870ff946d33</citedby><cites>FETCH-LOGICAL-c495t-44ebf7c54f96be491f596c150c9991aac51c61ef50f91f16a1367c870ff946d33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/1352458516635873$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/1352458516635873$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>230,314,776,780,881,21798,27901,27902,43597,43598</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26920376$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Yunpeng</creatorcontrib><creatorcontrib>Bos, Steffan D</creatorcontrib><creatorcontrib>Harbo, Hanne F</creatorcontrib><creatorcontrib>Thompson, Wesley K</creatorcontrib><creatorcontrib>Schork, Andrew J</creatorcontrib><creatorcontrib>Bettella, Francesco</creatorcontrib><creatorcontrib>Witoelar, Aree</creatorcontrib><creatorcontrib>Lie, Benedicte A</creatorcontrib><creatorcontrib>Li, Wen</creatorcontrib><creatorcontrib>McEvoy, Linda K</creatorcontrib><creatorcontrib>Djurovic, Srdjan</creatorcontrib><creatorcontrib>Desikan, Rahul S</creatorcontrib><creatorcontrib>Dale, Anders M</creatorcontrib><creatorcontrib>Andreassen, Ole A</creatorcontrib><title>Genetic overlap between multiple sclerosis and several cardiovascular disease risk factors</title><title>Multiple sclerosis</title><addtitle>Mult Scler</addtitle><description>Background:
Epidemiological findings suggest a relationship between multiple sclerosis (MS) and cardiovascular disease (CVD) risk factors, although the nature of this relationship is not well understood.
Objective:
We used genome-wide association study (GWAS) data to identify shared genetic factors (pleiotropy) between MS and CVD risk factors.
Methods:
Using summary statistics from a large, recent GWAS (total n > 250,000 individuals), we investigated overlap in single nucleotide polymorphisms (SNPs) associated with MS and a number of CVD risk factors including triglycerides (TG), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, body mass index, waist-to-hip ratio, type 2 diabetes, systolic blood pressure, and C-reactive protein level.
Results and conclusion:
Using conditional enrichment plots, we found 30-fold enrichment of MS SNPs for different levels of association with LDL and TG SNPs, with a corresponding reduction in conditional false discovery rate (FDR). We identified 133 pleiotropic loci outside the extended major histocompatibility complex with conditional FDR < 0.01, of which 65 are novel. These pleiotropic loci were located on 21 different chromosomes. Our findings point to overlapping pathobiology between clinically diagnosed MS and cardiovascular risk factors and identify novel common variants associated with increased MS risk.</description><subject>Cardiovascular disease</subject><subject>Cardiovascular Diseases - blood</subject><subject>Cardiovascular Diseases - epidemiology</subject><subject>Cardiovascular Diseases - genetics</subject><subject>Cardiovascular Diseases - physiopathology</subject><subject>Genetic Loci</subject><subject>Genetic Pleiotropy</subject><subject>Genome-Wide Association Study</subject><subject>Health risk assessment</subject><subject>Humans</subject><subject>Low density lipoprotein</subject><subject>Multiple sclerosis</subject><subject>Multiple Sclerosis - genetics</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Risk Factors</subject><issn>1352-4585</issn><issn>1477-0970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc9rFTEQx4MotlbvnkrAi5etyebX5lKQUluh4EUvXkJedlLT5m1eM7uv-N-b8mppC4KnCXw_853JfAl5z9kR58Z84kL1Ug2Kay3UYMQLss-lMR2zhr1s7yZ3d_oeeYN4xRgzRqjXZK_XtmfC6H3y8wwmmFOgZQs1-w1dwXwLMNH1kue0yUAxZKgFE1I_jRShcT7T4OuYytZjWLKvdEwIHoHWhNc0-jCXim_Jq-gzwrv7ekB-fDn9fnLeXXw7-3ry-aIL0qq5kxJW0QQlo9UrkJZHZXXgigVrLfc-KB40h6hYbBrXngttwmBYjFbqUYgDcrzz3SyrNYwBprlt6DY1rX397YpP7qkypV_usmydYoxbYZrBx3uDWm4WwNmtEwbI2U9QFnR8UIoNjEv7H2ivtRIDGxr64Rl6VZY6tUs0qoUk5SD7RrEdFdqNsUJ82Jszd5exe55xazl8_N-Hhr-hNqDbAegv4dHUfxn-AUZOr4Y</recordid><startdate>20161201</startdate><enddate>20161201</enddate><creator>Wang, Yunpeng</creator><creator>Bos, Steffan D</creator><creator>Harbo, Hanne F</creator><creator>Thompson, Wesley K</creator><creator>Schork, Andrew J</creator><creator>Bettella, Francesco</creator><creator>Witoelar, Aree</creator><creator>Lie, Benedicte A</creator><creator>Li, Wen</creator><creator>McEvoy, Linda K</creator><creator>Djurovic, Srdjan</creator><creator>Desikan, Rahul S</creator><creator>Dale, Anders M</creator><creator>Andreassen, Ole A</creator><general>SAGE Publications</general><general>Sage Publications 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>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20161201</creationdate><title>Genetic overlap between multiple sclerosis and several cardiovascular disease risk factors</title><author>Wang, Yunpeng ; Bos, Steffan D ; Harbo, Hanne F ; Thompson, Wesley K ; Schork, Andrew J ; Bettella, Francesco ; Witoelar, Aree ; Lie, Benedicte A ; Li, Wen ; McEvoy, Linda K ; Djurovic, Srdjan ; Desikan, Rahul S ; Dale, Anders M ; Andreassen, Ole A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-44ebf7c54f96be491f596c150c9991aac51c61ef50f91f16a1367c870ff946d33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Cardiovascular disease</topic><topic>Cardiovascular Diseases - blood</topic><topic>Cardiovascular Diseases - epidemiology</topic><topic>Cardiovascular Diseases - genetics</topic><topic>Cardiovascular Diseases - physiopathology</topic><topic>Genetic Loci</topic><topic>Genetic Pleiotropy</topic><topic>Genome-Wide Association Study</topic><topic>Health risk assessment</topic><topic>Humans</topic><topic>Low density lipoprotein</topic><topic>Multiple sclerosis</topic><topic>Multiple Sclerosis - genetics</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Risk Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Yunpeng</creatorcontrib><creatorcontrib>Bos, Steffan D</creatorcontrib><creatorcontrib>Harbo, Hanne F</creatorcontrib><creatorcontrib>Thompson, Wesley K</creatorcontrib><creatorcontrib>Schork, Andrew J</creatorcontrib><creatorcontrib>Bettella, Francesco</creatorcontrib><creatorcontrib>Witoelar, Aree</creatorcontrib><creatorcontrib>Lie, Benedicte A</creatorcontrib><creatorcontrib>Li, Wen</creatorcontrib><creatorcontrib>McEvoy, Linda K</creatorcontrib><creatorcontrib>Djurovic, Srdjan</creatorcontrib><creatorcontrib>Desikan, Rahul S</creatorcontrib><creatorcontrib>Dale, Anders M</creatorcontrib><creatorcontrib>Andreassen, Ole A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Multiple sclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yunpeng</au><au>Bos, Steffan D</au><au>Harbo, Hanne F</au><au>Thompson, Wesley K</au><au>Schork, Andrew J</au><au>Bettella, Francesco</au><au>Witoelar, Aree</au><au>Lie, Benedicte A</au><au>Li, Wen</au><au>McEvoy, Linda K</au><au>Djurovic, Srdjan</au><au>Desikan, Rahul S</au><au>Dale, Anders M</au><au>Andreassen, Ole A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic overlap between multiple sclerosis and several cardiovascular disease risk factors</atitle><jtitle>Multiple sclerosis</jtitle><addtitle>Mult Scler</addtitle><date>2016-12-01</date><risdate>2016</risdate><volume>22</volume><issue>14</issue><spage>1783</spage><epage>1793</epage><pages>1783-1793</pages><issn>1352-4585</issn><eissn>1477-0970</eissn><abstract>Background:
Epidemiological findings suggest a relationship between multiple sclerosis (MS) and cardiovascular disease (CVD) risk factors, although the nature of this relationship is not well understood.
Objective:
We used genome-wide association study (GWAS) data to identify shared genetic factors (pleiotropy) between MS and CVD risk factors.
Methods:
Using summary statistics from a large, recent GWAS (total n > 250,000 individuals), we investigated overlap in single nucleotide polymorphisms (SNPs) associated with MS and a number of CVD risk factors including triglycerides (TG), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, body mass index, waist-to-hip ratio, type 2 diabetes, systolic blood pressure, and C-reactive protein level.
Results and conclusion:
Using conditional enrichment plots, we found 30-fold enrichment of MS SNPs for different levels of association with LDL and TG SNPs, with a corresponding reduction in conditional false discovery rate (FDR). We identified 133 pleiotropic loci outside the extended major histocompatibility complex with conditional FDR < 0.01, of which 65 are novel. These pleiotropic loci were located on 21 different chromosomes. Our findings point to overlapping pathobiology between clinically diagnosed MS and cardiovascular risk factors and identify novel common variants associated with increased MS risk.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>26920376</pmid><doi>10.1177/1352458516635873</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Multiple sclerosis, 2016-12, Vol.22 (14), p.1783-1793 |
| issn | 1352-4585 1477-0970 |
| language | eng |
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| source | MEDLINE; SAGE Complete |
| subjects | Cardiovascular disease Cardiovascular Diseases - blood Cardiovascular Diseases - epidemiology Cardiovascular Diseases - genetics Cardiovascular Diseases - physiopathology Genetic Loci Genetic Pleiotropy Genome-Wide Association Study Health risk assessment Humans Low density lipoprotein Multiple sclerosis Multiple Sclerosis - genetics Polymorphism, Single Nucleotide Risk Factors |
| title | Genetic overlap between multiple sclerosis and several cardiovascular disease risk factors |
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