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A 3-SNP gene risk score and a metabolic risk score both predict hypertriglyceridemia and cardiovascular disease risk
Evidence on the causal link between plasma triglyceride (TG) levels and risk for cardiovascular disease (CVD) has recently emerged. Individuals with the metabolic syndrome have an increased risk for acquiring elevated TG levels later in life. Moreover, common DNA sequence variations in genes affecti...
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| Published in: | Journal of clinical lipidology 2019-05, Vol.13 (3), p.492-501 |
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| container_issue | 3 |
| container_start_page | 492 |
| container_title | Journal of clinical lipidology |
| container_volume | 13 |
| creator | Verbeek, Rutger Oldoni, Federico Surendran, R. Preethi Zwinderman, Ailko H. Khaw, Kay T. Stroes, Erik S.G. Wareham, Nick J. Boekholdt, S. Matthijs Dallinga-Thie, Geesje M. |
| description | Evidence on the causal link between plasma triglyceride (TG) levels and risk for cardiovascular disease (CVD) has recently emerged. Individuals with the metabolic syndrome have an increased risk for acquiring elevated TG levels later in life. Moreover, common DNA sequence variations in genes affecting TG levels identify individuals at risk for elevated plasma TG levels.
We evaluated whether a 3-single nucleotide polymorphism (SNP) TG gene risk score (GRS) and a metabolic risk score (MetRS) both improved CVD risk prediction.
A 3-SNP GRS and MetRS were generated in the EPIC-Norfolk cohort (n = 20,074) based on 3 SNPs in LPL and APOA5 or the number of Metabolic Syndrome criteria present (maximum 5), respectively. The associations between the 3-SNP GRS, MetRS, TG levels, and CVD risk were evaluated.
The 3-SNP GRS and MetRS were both linearly associated with plasma TG levels, that is, +0.25 mmol/L [95% CI 0.22–0.27] per allele change (P |
| doi_str_mv | 10.1016/j.jacl.2019.02.005 |
| format | article |
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We evaluated whether a 3-single nucleotide polymorphism (SNP) TG gene risk score (GRS) and a metabolic risk score (MetRS) both improved CVD risk prediction.
A 3-SNP GRS and MetRS were generated in the EPIC-Norfolk cohort (n = 20,074) based on 3 SNPs in LPL and APOA5 or the number of Metabolic Syndrome criteria present (maximum 5), respectively. The associations between the 3-SNP GRS, MetRS, TG levels, and CVD risk were evaluated.
The 3-SNP GRS and MetRS were both linearly associated with plasma TG levels, that is, +0.25 mmol/L [95% CI 0.22–0.27] per allele change (P < .001) and +0.72 mmol/L [95% CI 0.70–0.73] per increase of number of metabolic syndrome risk score points (P < .001), respectively. We observed a positive association between the 3-SNP GRS and the risk of CVD with an adjusted hazard ratio (HR) of 1.35 [95% CI 1.04–1.74] for the highest versus the lowest GRS, which was independent of the MetRS. For the MetRS, the adjusted HR was 2.03 [95% CI 1.73–2.40] for the highest versus the lowest MetRS.
Both the 3-SNP GRS and the MetRS are associated with increased plasma TG levels and increased risk for CVD.
•Metabolic risk score is associated with plasma triglycerides.•Gene risk score is associated with plasma triglycerides.•Metabolic risk score and TG-gene risk score are both associated with increased CVD risk.</description><identifier>ISSN: 1933-2874</identifier><identifier>EISSN: 1876-4789</identifier><identifier>DOI: 10.1016/j.jacl.2019.02.005</identifier><identifier>PMID: 30910668</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Aged ; APOA5 ; Cardiovascular disease ; Cardiovascular Diseases - blood ; Cardiovascular Diseases - genetics ; Cardiovascular Diseases - metabolism ; Cohort Studies ; Female ; Genetic Predisposition to Disease - genetics ; Humans ; Hypertriglyceridemia - blood ; Hypertriglyceridemia - genetics ; Hypertriglyceridemia - metabolism ; LPL ; Male ; Metabolic syndrome ; Middle Aged ; Polymorphism, Single Nucleotide ; Risk Assessment ; Triglycerides ; Triglycerides - blood ; Triglycerides - genetics</subject><ispartof>Journal of clinical lipidology, 2019-05, Vol.13 (3), p.492-501</ispartof><rights>2019 National Lipid Association</rights><rights>Copyright © 2019 National Lipid Association. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-ba9967c5699235a06d1d91dea7cef4285d9adcf0627eed8f3ff8cab0aa80941b3</citedby><cites>FETCH-LOGICAL-c455t-ba9967c5699235a06d1d91dea7cef4285d9adcf0627eed8f3ff8cab0aa80941b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30910668$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Verbeek, Rutger</creatorcontrib><creatorcontrib>Oldoni, Federico</creatorcontrib><creatorcontrib>Surendran, R. Preethi</creatorcontrib><creatorcontrib>Zwinderman, Ailko H.</creatorcontrib><creatorcontrib>Khaw, Kay T.</creatorcontrib><creatorcontrib>Stroes, Erik S.G.</creatorcontrib><creatorcontrib>Wareham, Nick J.</creatorcontrib><creatorcontrib>Boekholdt, S. Matthijs</creatorcontrib><creatorcontrib>Dallinga-Thie, Geesje M.</creatorcontrib><title>A 3-SNP gene risk score and a metabolic risk score both predict hypertriglyceridemia and cardiovascular disease risk</title><title>Journal of clinical lipidology</title><addtitle>J Clin Lipidol</addtitle><description>Evidence on the causal link between plasma triglyceride (TG) levels and risk for cardiovascular disease (CVD) has recently emerged. Individuals with the metabolic syndrome have an increased risk for acquiring elevated TG levels later in life. Moreover, common DNA sequence variations in genes affecting TG levels identify individuals at risk for elevated plasma TG levels.
We evaluated whether a 3-single nucleotide polymorphism (SNP) TG gene risk score (GRS) and a metabolic risk score (MetRS) both improved CVD risk prediction.
A 3-SNP GRS and MetRS were generated in the EPIC-Norfolk cohort (n = 20,074) based on 3 SNPs in LPL and APOA5 or the number of Metabolic Syndrome criteria present (maximum 5), respectively. The associations between the 3-SNP GRS, MetRS, TG levels, and CVD risk were evaluated.
The 3-SNP GRS and MetRS were both linearly associated with plasma TG levels, that is, +0.25 mmol/L [95% CI 0.22–0.27] per allele change (P < .001) and +0.72 mmol/L [95% CI 0.70–0.73] per increase of number of metabolic syndrome risk score points (P < .001), respectively. We observed a positive association between the 3-SNP GRS and the risk of CVD with an adjusted hazard ratio (HR) of 1.35 [95% CI 1.04–1.74] for the highest versus the lowest GRS, which was independent of the MetRS. For the MetRS, the adjusted HR was 2.03 [95% CI 1.73–2.40] for the highest versus the lowest MetRS.
Both the 3-SNP GRS and the MetRS are associated with increased plasma TG levels and increased risk for CVD.
•Metabolic risk score is associated with plasma triglycerides.•Gene risk score is associated with plasma triglycerides.•Metabolic risk score and TG-gene risk score are both associated with increased CVD risk.</description><subject>Adult</subject><subject>Aged</subject><subject>APOA5</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular Diseases - blood</subject><subject>Cardiovascular Diseases - genetics</subject><subject>Cardiovascular Diseases - metabolism</subject><subject>Cohort Studies</subject><subject>Female</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Humans</subject><subject>Hypertriglyceridemia - blood</subject><subject>Hypertriglyceridemia - genetics</subject><subject>Hypertriglyceridemia - metabolism</subject><subject>LPL</subject><subject>Male</subject><subject>Metabolic syndrome</subject><subject>Middle Aged</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Risk Assessment</subject><subject>Triglycerides</subject><subject>Triglycerides - blood</subject><subject>Triglycerides - genetics</subject><issn>1933-2874</issn><issn>1876-4789</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kUuLFDEUhQtRnIf-AReSpZsq86ikKiDCMIyOMKigrsOt5FZ32qpKm6Qb-t-btsdh3LhK4J5z7uV8VfWK0YZRpt5umg3YqeGU6YbyhlL5pDpnfafqtuv10_LXQtS879qz6iKlTRHIjsrn1ZmgmlGl-vMqXxFRf_v8laxwQRJ9-kmSDREJLI4AmTHDECZvH4-GkNdkG9F5m8n6sMWYo19NB4vRO5w9_DFbiM6HPSS7myAS5xNCOq14UT0bYUr48v69rH58uPl-fVvfffn46frqrratlLkeQGvVWam05kICVY45zRxCZ3FseS-dBmdHqniH6PpRjGNvYaAAPdUtG8Rl9f6Uu90NMzqLS44wmW30M8SDCeDNv5PFr80q7E0nWiqFKgFv7gNi-LXDlM3sk8VpggXDLhnOdGlaMEqLlJ-kNoaUIo4Paxg1R1xmY464zBGXodwUGsX0-vGBD5a_fIrg3UmApaa9x2iS9bjY0n1Em40L_n_5vwFx16nG</recordid><startdate>20190501</startdate><enddate>20190501</enddate><creator>Verbeek, Rutger</creator><creator>Oldoni, Federico</creator><creator>Surendran, R. Preethi</creator><creator>Zwinderman, Ailko H.</creator><creator>Khaw, Kay T.</creator><creator>Stroes, Erik S.G.</creator><creator>Wareham, Nick J.</creator><creator>Boekholdt, S. Matthijs</creator><creator>Dallinga-Thie, Geesje M.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><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><scope>5PM</scope></search><sort><creationdate>20190501</creationdate><title>A 3-SNP gene risk score and a metabolic risk score both predict hypertriglyceridemia and cardiovascular disease risk</title><author>Verbeek, Rutger ; Oldoni, Federico ; Surendran, R. Preethi ; Zwinderman, Ailko H. ; Khaw, Kay T. ; Stroes, Erik S.G. ; Wareham, Nick J. ; Boekholdt, S. Matthijs ; Dallinga-Thie, Geesje M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-ba9967c5699235a06d1d91dea7cef4285d9adcf0627eed8f3ff8cab0aa80941b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Aged</topic><topic>APOA5</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular Diseases - blood</topic><topic>Cardiovascular Diseases - genetics</topic><topic>Cardiovascular Diseases - metabolism</topic><topic>Cohort Studies</topic><topic>Female</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Humans</topic><topic>Hypertriglyceridemia - blood</topic><topic>Hypertriglyceridemia - genetics</topic><topic>Hypertriglyceridemia - metabolism</topic><topic>LPL</topic><topic>Male</topic><topic>Metabolic syndrome</topic><topic>Middle Aged</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Risk Assessment</topic><topic>Triglycerides</topic><topic>Triglycerides - blood</topic><topic>Triglycerides - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Verbeek, Rutger</creatorcontrib><creatorcontrib>Oldoni, Federico</creatorcontrib><creatorcontrib>Surendran, R. Preethi</creatorcontrib><creatorcontrib>Zwinderman, Ailko H.</creatorcontrib><creatorcontrib>Khaw, Kay T.</creatorcontrib><creatorcontrib>Stroes, Erik S.G.</creatorcontrib><creatorcontrib>Wareham, Nick J.</creatorcontrib><creatorcontrib>Boekholdt, S. Matthijs</creatorcontrib><creatorcontrib>Dallinga-Thie, Geesje M.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of clinical lipidology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Verbeek, Rutger</au><au>Oldoni, Federico</au><au>Surendran, R. Preethi</au><au>Zwinderman, Ailko H.</au><au>Khaw, Kay T.</au><au>Stroes, Erik S.G.</au><au>Wareham, Nick J.</au><au>Boekholdt, S. Matthijs</au><au>Dallinga-Thie, Geesje M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A 3-SNP gene risk score and a metabolic risk score both predict hypertriglyceridemia and cardiovascular disease risk</atitle><jtitle>Journal of clinical lipidology</jtitle><addtitle>J Clin Lipidol</addtitle><date>2019-05-01</date><risdate>2019</risdate><volume>13</volume><issue>3</issue><spage>492</spage><epage>501</epage><pages>492-501</pages><issn>1933-2874</issn><eissn>1876-4789</eissn><abstract>Evidence on the causal link between plasma triglyceride (TG) levels and risk for cardiovascular disease (CVD) has recently emerged. Individuals with the metabolic syndrome have an increased risk for acquiring elevated TG levels later in life. Moreover, common DNA sequence variations in genes affecting TG levels identify individuals at risk for elevated plasma TG levels.
We evaluated whether a 3-single nucleotide polymorphism (SNP) TG gene risk score (GRS) and a metabolic risk score (MetRS) both improved CVD risk prediction.
A 3-SNP GRS and MetRS were generated in the EPIC-Norfolk cohort (n = 20,074) based on 3 SNPs in LPL and APOA5 or the number of Metabolic Syndrome criteria present (maximum 5), respectively. The associations between the 3-SNP GRS, MetRS, TG levels, and CVD risk were evaluated.
The 3-SNP GRS and MetRS were both linearly associated with plasma TG levels, that is, +0.25 mmol/L [95% CI 0.22–0.27] per allele change (P < .001) and +0.72 mmol/L [95% CI 0.70–0.73] per increase of number of metabolic syndrome risk score points (P < .001), respectively. We observed a positive association between the 3-SNP GRS and the risk of CVD with an adjusted hazard ratio (HR) of 1.35 [95% CI 1.04–1.74] for the highest versus the lowest GRS, which was independent of the MetRS. For the MetRS, the adjusted HR was 2.03 [95% CI 1.73–2.40] for the highest versus the lowest MetRS.
Both the 3-SNP GRS and the MetRS are associated with increased plasma TG levels and increased risk for CVD.
•Metabolic risk score is associated with plasma triglycerides.•Gene risk score is associated with plasma triglycerides.•Metabolic risk score and TG-gene risk score are both associated with increased CVD risk.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>30910668</pmid><doi>10.1016/j.jacl.2019.02.005</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | ScienceDirect Freedom Collection |
| subjects | Adult Aged APOA5 Cardiovascular disease Cardiovascular Diseases - blood Cardiovascular Diseases - genetics Cardiovascular Diseases - metabolism Cohort Studies Female Genetic Predisposition to Disease - genetics Humans Hypertriglyceridemia - blood Hypertriglyceridemia - genetics Hypertriglyceridemia - metabolism LPL Male Metabolic syndrome Middle Aged Polymorphism, Single Nucleotide Risk Assessment Triglycerides Triglycerides - blood Triglycerides - genetics |
| title | A 3-SNP gene risk score and a metabolic risk score both predict hypertriglyceridemia and cardiovascular disease risk |
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