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Bivariate GWAS Scan Identifies Six Novel Loci Associated with Lipid Levels and Coronary Artery Disease
Plasma lipid levels are heritable and genetically associated with risk of coronary artery disease (CAD). However, genome-wide association studies (GWAS) routinely perform association studies of these traits independently of one another. Joint GWAS for two related phenotypes can lead to a higher-powe...
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Published in: | Human heredity 2018-06, Vol.83 (1), p.50 |
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description | Plasma lipid levels are heritable and genetically associated with risk of coronary artery disease (CAD). However, genome-wide association studies (GWAS) routinely perform association studies of these traits independently of one another. Joint GWAS for two related phenotypes can lead to a higher-powered analysis to detect variants contributing to both traits. We performed a bivariate GWAS to discover novel loci associated with heart disease, using a CAD Meta-Analysis (122,733 cases and 424,528 controls), and lipid traits, using data from the Global Lipid Genetics Consortium (188,577 subjects). We identified six novel genome-wide significant loci, three which were associated with Triglycerides and CAD, two which were associated with LDL cholesterol and CAD, and one associated with Total Cholesterol and CAD. At several of our loci, the GWAS signals colocalize with expression level associations for one or more genes, indicating that these loci may be affecting disease risk through regulatory activity. |
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However, genome-wide association studies (GWAS) routinely perform association studies of these traits independently of one another. Joint GWAS for two related phenotypes can lead to a higher-powered analysis to detect variants contributing to both traits. We performed a bivariate GWAS to discover novel loci associated with heart disease, using a CAD Meta-Analysis (122,733 cases and 424,528 controls), and lipid traits, using data from the Global Lipid Genetics Consortium (188,577 subjects). We identified six novel genome-wide significant loci, three which were associated with Triglycerides and CAD, two which were associated with LDL cholesterol and CAD, and one associated with Total Cholesterol and CAD. At several of our loci, the GWAS signals colocalize with expression level associations for one or more genes, indicating that these loci may be affecting disease risk through regulatory activity.</description><identifier>ISSN: 0001-5652</identifier><identifier>EISSN: 1423-0062</identifier><language>eng</language><publisher>Basel: S. Karger AG</publisher><subject>Cardiovascular disease ; Cholesterol ; Coronary artery ; Coronary artery disease ; Gene loci ; Genome-wide association studies ; Genomes ; Genomics ; Genotype & phenotype ; Heart diseases ; Lipids ; Low density lipoprotein ; Phenotypes ; Plasma ; Triglycerides</subject><ispartof>Human heredity, 2018-06, Vol.83 (1), p.50</ispartof><rights>Copyright S. 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We performed a bivariate GWAS to discover novel loci associated with heart disease, using a CAD Meta-Analysis (122,733 cases and 424,528 controls), and lipid traits, using data from the Global Lipid Genetics Consortium (188,577 subjects). We identified six novel genome-wide significant loci, three which were associated with Triglycerides and CAD, two which were associated with LDL cholesterol and CAD, and one associated with Total Cholesterol and CAD. At several of our loci, the GWAS signals colocalize with expression level associations for one or more genes, indicating that these loci may be affecting disease risk through regulatory activity.</description><subject>Cardiovascular disease</subject><subject>Cholesterol</subject><subject>Coronary artery</subject><subject>Coronary artery disease</subject><subject>Gene loci</subject><subject>Genome-wide association studies</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Genotype & phenotype</subject><subject>Heart diseases</subject><subject>Lipids</subject><subject>Low density lipoprotein</subject><subject>Phenotypes</subject><subject>Plasma</subject><subject>Triglycerides</subject><issn>0001-5652</issn><issn>1423-0062</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNqNyssKwjAQheEgCtbLOwy4LsTUVl3Wu1DcVHApwU5xRBLNxNvbm4UP4OrncL6GiIYjlcRSZqopIinlME6zVLVFh_kS5kSOk0jUM3pqR9ojrA95CeVJG9hWaDzVhAwlvWFnn3iFwp4IcuaQoCt4kT9DQTeqoMAAGLSpYG6dNdp9IHceQxbEqBl7olXrK2P_164YrJb7-Sa-OXt_IPvjxT6cCddRyalU2Uil0-Q_9QX3PEb_</recordid><startdate>20180601</startdate><enddate>20180601</enddate><creator>Siewert, K</creator><creator>Voight, B</creator><general>S. Karger AG</general><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20180601</creationdate><title>Bivariate GWAS Scan Identifies Six Novel Loci Associated with Lipid Levels and Coronary Artery Disease</title><author>Siewert, K ; Voight, B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_journals_20902642593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Cardiovascular disease</topic><topic>Cholesterol</topic><topic>Coronary artery</topic><topic>Coronary artery disease</topic><topic>Gene loci</topic><topic>Genome-wide association studies</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Genotype & phenotype</topic><topic>Heart diseases</topic><topic>Lipids</topic><topic>Low density lipoprotein</topic><topic>Phenotypes</topic><topic>Plasma</topic><topic>Triglycerides</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Siewert, K</creatorcontrib><creatorcontrib>Voight, B</creatorcontrib><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Human heredity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Siewert, K</au><au>Voight, B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bivariate GWAS Scan Identifies Six Novel Loci Associated with Lipid Levels and Coronary Artery Disease</atitle><jtitle>Human heredity</jtitle><date>2018-06-01</date><risdate>2018</risdate><volume>83</volume><issue>1</issue><spage>50</spage><pages>50-</pages><issn>0001-5652</issn><eissn>1423-0062</eissn><abstract>Plasma lipid levels are heritable and genetically associated with risk of coronary artery disease (CAD). However, genome-wide association studies (GWAS) routinely perform association studies of these traits independently of one another. Joint GWAS for two related phenotypes can lead to a higher-powered analysis to detect variants contributing to both traits. We performed a bivariate GWAS to discover novel loci associated with heart disease, using a CAD Meta-Analysis (122,733 cases and 424,528 controls), and lipid traits, using data from the Global Lipid Genetics Consortium (188,577 subjects). We identified six novel genome-wide significant loci, three which were associated with Triglycerides and CAD, two which were associated with LDL cholesterol and CAD, and one associated with Total Cholesterol and CAD. At several of our loci, the GWAS signals colocalize with expression level associations for one or more genes, indicating that these loci may be affecting disease risk through regulatory activity.</abstract><cop>Basel</cop><pub>S. Karger AG</pub></addata></record> |
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subjects | Cardiovascular disease Cholesterol Coronary artery Coronary artery disease Gene loci Genome-wide association studies Genomes Genomics Genotype & phenotype Heart diseases Lipids Low density lipoprotein Phenotypes Plasma Triglycerides |
title | Bivariate GWAS Scan Identifies Six Novel Loci Associated with Lipid Levels and Coronary Artery Disease |
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