Abstract
PURPOSE: Because multiple genetic variants influence risk for coronary heart disease, we combined multiple variants that had been associated with coronary heart disease in several studies into a genetic risk score and asked whether a high genetic risk score would be significantly associated with coronary heart disease after accounting for traditional risk factors. METHODS: We considered five variants that were associated with coronary heart disease in two studies and confirmed in the Atherosclerosis Risk in Communities study: rs20455 (KIF6), rs3900940 (MYH15), rs7439293 (PALLD), rs2298566 (SNX19), and rs1010 (VAMP8). We calculated a genetic risk score for each Atherosclerosis Risk in Communities study participant and estimated the hazard ratio for incident coronary heart disease of a high genetic risk score (compared with not-high) in Cox models that adjusted for traditional risk factors during a median of 13 years of follow-up. RESULTS: For white participants with a high genetic risk score (4% of the 9129 whites), compared with those without a high genetic risk score, the hazard ratio for incident coronary heart disease was 1.57 (95% confidence interval 1.21-2.04; P = 0.001). Internal validation using bootstrap samples estimated that a hazard ratio of 1.43 could be expected in external populations. CONCLUSIONS: After adjusting for traditional risk factors, those with a high genetic risk score had a 57% increased risk of incident coronary heart disease in the Atherosclerosis Risk in Communities study.
Original language | English (US) |
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Pages (from-to) | 682-689 |
Number of pages | 8 |
Journal | Genetics in Medicine |
Volume | 9 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2007 |
Keywords
- Atherosclerosis Risk in Communities study
- Complex disease
- Coronary heart disease
- Genetic risk score
- Single nucleotide polymorphism
- Variant