Five common gene variants identify elevated genetic risk for coronary heart disease.
OBJECTIVE
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.
Bare
Lance A
LA
Celera, Alameda, California 94502, USA. Lance.Bare@celera.com
Morrison
Alanna C
AC
Rowland
Charles M
CM
Shiffman
Dov
D
Luke
May M
MM
Iakoubova
Olga A
OA
Kane
John P
JP
Malloy
Mary J
MJ
Ellis
Stephen G
SG
Pankow
James S
JS
Willerson
James T
JT
Devlin
James J
JJ
Boerwinkle
Eric
E
D000465:Algorithms; D016022:Case-Control Studies; D015331:Cohort Studies; D003327:Coronary Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models