A 3-SNP gene risk score and a metabolic risk score both predict hypertriglyceridemia and cardiovascular disease risk

Rutger Verbeek, Federico Oldoni, R. Preethi Surendran, Ailko H. Zwinderman, Kay T. Khaw, Erik S. G. Stroes, Nick J. Wareham, S. Matthijs Boekholdt, Geesje M. Dallinga-Thie

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: Both the 3-SNP GRS and the MetRS are associated with increased plasma TG levels and increased risk for CVD.
Original languageEnglish
Pages (from-to)492-501
JournalJournal of clinical lipidology
Volume13
Issue number3
DOIs
Publication statusPublished - 2019

Cite this

Verbeek, R., Oldoni, F., Surendran, R. P., Zwinderman, A. H., Khaw, K. T., Stroes, E. S. G., ... Dallinga-Thie, G. M. (2019). A 3-SNP gene risk score and a metabolic risk score both predict hypertriglyceridemia and cardiovascular disease risk. Journal of clinical lipidology, 13(3), 492-501. https://doi.org/10.1016/j.jacl.2019.02.005
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. / A 3-SNP gene risk score and a metabolic risk score both predict hypertriglyceridemia and cardiovascular disease risk. In: Journal of clinical lipidology. 2019 ; Vol. 13, No. 3. pp. 492-501.
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title = "A 3-SNP gene risk score and a metabolic risk score both predict hypertriglyceridemia and cardiovascular disease risk",
abstract = "Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: Both the 3-SNP GRS and the MetRS are associated with increased plasma TG levels and increased risk for CVD.",
author = "Rutger Verbeek and Federico Oldoni and Surendran, {R. Preethi} and Zwinderman, {Ailko H.} and Khaw, {Kay T.} and Stroes, {Erik S. G.} and Wareham, {Nick J.} and Boekholdt, {S. Matthijs} and Dallinga-Thie, {Geesje M.}",
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Verbeek, R, Oldoni, F, Surendran, RP, Zwinderman, AH, Khaw, KT, Stroes, ESG, Wareham, NJ, Boekholdt, SM & Dallinga-Thie, GM 2019, 'A 3-SNP gene risk score and a metabolic risk score both predict hypertriglyceridemia and cardiovascular disease risk' Journal of clinical lipidology, vol. 13, no. 3, pp. 492-501. https://doi.org/10.1016/j.jacl.2019.02.005

A 3-SNP gene risk score and a metabolic risk score both predict hypertriglyceridemia and cardiovascular disease risk. / 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.

In: Journal of clinical lipidology, Vol. 13, No. 3, 2019, p. 492-501.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - A 3-SNP gene risk score and a metabolic risk score both predict hypertriglyceridemia and cardiovascular disease risk

AU - Verbeek, Rutger

AU - Oldoni, Federico

AU - Surendran, R. Preethi

AU - Zwinderman, Ailko H.

AU - Khaw, Kay T.

AU - Stroes, Erik S. G.

AU - Wareham, Nick J.

AU - Boekholdt, S. Matthijs

AU - Dallinga-Thie, Geesje M.

PY - 2019

Y1 - 2019

N2 - Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: Both the 3-SNP GRS and the MetRS are associated with increased plasma TG levels and increased risk for CVD.

AB - Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: Both the 3-SNP GRS and the MetRS are associated with increased plasma TG levels and increased risk for CVD.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85063226015&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/30910668

U2 - 10.1016/j.jacl.2019.02.005

DO - 10.1016/j.jacl.2019.02.005

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JO - Journal of clinical lipidology

JF - Journal of clinical lipidology

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