Journal
GENETICS IN MEDICINE
Volume 9, Issue 10, Pages 682-689Publisher
NATURE PUBLISHING GROUP
DOI: 10.1097/GIM.0b013e318156fb62
Keywords
atherosclerosis risk in communities study; coronaty heart disease; genetic risk score; variant; single nucleotide polymorphism; complex disease
Categories
Funding
- NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55022, N01-HC-55020, N01-HC-55021, N01-HC-55018, N01-HC-55019] Funding Source: Medline
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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.
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