A genotype score of nine validated single-nucleotide polymorphisms as an independent risk factor for incident cardiovascular disease
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The study was aimed to test the hypothesis that a combination of common single-nucleotide polymorphisms (SNPs) which individually modestly affect LDL-cholesterol and HDL-cholesterol may contribute as a cluster to the risk of cardiovascular disease. To this end, SNPs at nine loci were studied in 5,414 subjects from the cardiovascular cohort of the Malmö Diet and Cancer Study. Firstly, the association between SNPs and either LDL- or HDL-cholesterol was validated and secondly, a genotype score was created on the basis of the number of unfavourable alleles. Cox proportional hazards models were then used to determine the time to first cardiovascular event in relation to genotype score. All nine SNPs showed replication of association, with levels of either LDL- or HDL-cholesterol, the level of LDL-cholesterol increasing and that of HDL-cholesterol decreasing with increasing genotype scores. During a median follow-up of 10.6 years, 238 subjects had a cardiovascular event. In models adjusted for covariates including baseline lipid levels, the genotype was associated with incident cardiovascular events. Although the genotype score did not improve overall risk prediction, there was a significant improvement in risk stratification when using models that included the genotype score. The authors conclude that a genotype score of nine validated SNPs that are associated with LDL- and HDL-cholesterol is an independent risk factor for incident cardiovascular disease.
Abstract
