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

doi: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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

5 Citations (Scopus)

164 Downloads (Pure)

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

CONCLUSION: Both the 3-SNP GRS and the MetRS are associated with increased plasma TG levels and increased risk for CVD. 2019 National Lipid Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Original language	English
Pages (from-to)	492-501
Number of pages	10
Journal	Journal of Clinical Lipidology
Volume	13
Issue number	3
DOIs	https://doi.org/10.1016/j.jacl.2019.02.005
Publication status	Published - Jun-2019

Keywords

Triglycerides
APOA5
LPL
Metabolic syndrome
Cardiovascular disease
DENSITY-LIPOPROTEIN CHOLESTEROL
CORONARY-HEART-DISEASE
TRIGLYCERIDE-RICH LIPOPROTEINS
GENOME-WIDE ASSOCIATION
OF-FUNCTION MUTATIONS
NONFASTING TRIGLYCERIDES
REMNANT CHOLESTEROL
EPIC-NORFOLK
MYOCARDIAL-INFARCTION
COMMON VARIANTS

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A 3-SNP gene risk score and a metabolic risk score both predict hypertriglyceridemia and cardiovascular disease riskFinal publisher's version, 340 KBLicence: CC BY-NC-ND

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@article{d35924a0297246dcbc6db7336f03228e,

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 (PCONCLUSION: Both the 3-SNP GRS and the MetRS are associated with increased plasma TG levels and increased risk for CVD. 2019 National Lipid Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).",

keywords = "Triglycerides, APOA5, LPL, Metabolic syndrome, Cardiovascular disease, DENSITY-LIPOPROTEIN CHOLESTEROL, CORONARY-HEART-DISEASE, TRIGLYCERIDE-RICH LIPOPROTEINS, GENOME-WIDE ASSOCIATION, OF-FUNCTION MUTATIONS, NONFASTING TRIGLYCERIDES, REMNANT CHOLESTEROL, EPIC-NORFOLK, MYOCARDIAL-INFARCTION, COMMON VARIANTS",

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.\}",

year = "2019",

month = jun,

doi = "10.1016/j.jacl.2019.02.005",

language = "English",

volume = "13",

pages = "492--501",

journal = "Journal of Clinical Lipidology",

issn = "1933-2874",

publisher = "ELSEVIER SCIENCE INC",

number = "3",

}

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 - 2019/6

Y1 - 2019/6

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 (PCONCLUSION: Both the 3-SNP GRS and the MetRS are associated with increased plasma TG levels and increased risk for CVD. 2019 National Lipid Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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 (PCONCLUSION: Both the 3-SNP GRS and the MetRS are associated with increased plasma TG levels and increased risk for CVD. 2019 National Lipid Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

KW - Triglycerides

KW - APOA5

KW - LPL

KW - Metabolic syndrome

KW - Cardiovascular disease

KW - DENSITY-LIPOPROTEIN CHOLESTEROL

KW - CORONARY-HEART-DISEASE

KW - TRIGLYCERIDE-RICH LIPOPROTEINS

KW - GENOME-WIDE ASSOCIATION

KW - OF-FUNCTION MUTATIONS

KW - NONFASTING TRIGLYCERIDES

KW - REMNANT CHOLESTEROL

KW - EPIC-NORFOLK

KW - MYOCARDIAL-INFARCTION

KW - COMMON VARIANTS

U2 - 10.1016/j.jacl.2019.02.005

DO - 10.1016/j.jacl.2019.02.005

M3 - Article

SN - 1933-2874

VL - 13

SP - 492

EP - 501

JO - Journal of Clinical Lipidology

JF - Journal of Clinical Lipidology

IS - 3

ER -

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

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