Key result
The highest versus lowest 3-SNP gene risk score was associated with an increased risk of cardiovascular disease (HR 1.35; 95% CI 1.04-1.74), independent of the metabolic risk score.
Why the study?
Although plasma triglycerides are causally linked to cardiovascular disease risk and elevated by metabolic syndrome and genetic variants, whether a 3-SNP TG gene risk score and a metabolic risk score improve cardiovascular disease risk prediction remained to be evaluated.
Do a 3-SNP gene risk score and a metabolic risk score predict hypertriglyceridemia and cardiovascular disease risk?
Cohort (n=20,074)
Do a 3-SNP gene risk score and a metabolic risk score predict hypertriglyceridemia and cardiovascular disease risk?
Both a 3-SNP gene risk score and a metabolic risk score independently predict elevated plasma triglyceride levels and increased risk for cardiovascular disease.
TG GRS independently associates with CVD risk; leaves open whether it improves prediction beyond metabolic factors.
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.
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Verbeek et al. (2019) conducted a cohort in Cardiovascular disease (n=20,074). 3-SNP gene risk score (GRS) vs. Lowest GRS was evaluated on Cardiovascular disease risk (HR 1.35, 95% CI 1.04-1.74). The highest versus lowest 3-SNP gene risk score was associated with an increased risk of cardiovascular disease (HR 1.35; 95% CI 1.04-1.74), independent of the metabolic risk score.
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