|Lai, Chao Qiang|
Submitted to: Nutrition Metabolism and Cardiovascular Disease
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/16/2009
Publication Date: 6/5/2009
Citation: Junyent, M., Parnell, L.D., Lai, C., Ordovas, J.M., Tucker, K.L., Shen, J., Mattei, J., Smith, C., Lee, Y. 2009. A composite scoring of genotypes discriminates coronary heart disease risk beyond conventional risk factors in the Boston Puerto Rican Health Study. Nutrition Metabolism and Cardiovascular Disease.20(3):157-167. Interpretive Summary: Because different, single genetic variants can contribute a small degree of risk or protection for coronary heart disease (CHD), it is useful to examine genetic scores comprised of several variants. Thus, a genetic predisposition score (GPS) integrates the additive associations of a set of single genetic variants with CHD. We examined the consequences of the joint presence of a high GPS and conventional risk factors (CRFs) by studying eleven different genetic variants in 197 participants with prior CHD and 524 CHD-free subjects from the Boston Puerto Rican Health Study. Each of these eleven genetic variants contributed 1 unit, (for two copies of the high-risk version), 0.5 unit (for one copy of the high-risk version), or 0 units (for two copies of the low-risk version) to the GPS. Unsurprisingly, our results showed that persons with prior CHD scored higher in the GPS method than those who were CHD-free. The joint presence of a high GPS and each CRF was correlated with a significantly increased risk of CHD. Importantly, by comparing persons with low GPS to those with high GPS, we could assess the odds ratio of increased risk of CHD based on certain conventional lifestyle choices (tobacco or alcohol use, or physical activity) or disease markers (hypertension, dyslipidemia). All exerted a strong influence on risk of CHD. When the genetic predisposition score (GPS) is high (compared to low GPS scorers), the strongest odds ratios were observed for dyslipidemia and low physical activity (approx.3-fold greater risk of CHD), followed by those who take any amount of alcohol or tobacco (approx. 2.3-fold greater risk of CHD) and hypertension (approx. 1.9-fold greater risk of CHD). Thus, a simple genetic score that integrates the additive impact of eleven genetic variants may identify persons at increased risk of CHD beyond conventional risk factors.
Technical Abstract: Background: Few studies have examined the usefulness of genetic scores to identify subjects at increased risk for coronary heart disease (CHD). Using a genetic predisposition score (GPS), integrating the additive associations of a set of single nucleotide polymorphisms (SNPs) with CHD, we examined the consequences of the joint presence of a high GPS and conventional risk factors (CRFs). Methods: We studied eleven SNPs at eight loci in 197 participants with prior CHD and 524 CHD-free subjects from the Boston Puerto Rican Health Study. Each polymorphism contributed 1 unit (high-risk allele homozygous), 0.5 unit (heterozygous) and 0 units (low-risk allele homozygous) to the GPS. Odds ratio (OR) of CHD for those at high-risk defined by a GPS (>5) and simultaneous presence of an established CHD risk factor were estimated and compared with subjects at low-risk, for both the GPS and each non-genetic CHD risk factor. Results: The mean score was higher in participants with prior CHD than those CHD-free (P=0.015), and the multivariate OR for CHD with a score >5 was 2.90 (1.70-4.99; P<0.001). Joint presence of a high GPS and each CRF was associated with a significantly increased risk of CHD. Comparing participants with low GPS (</=5) to those with high GPS (reference value), the OR was 0.44(0.21-0.89) for ever smokers, 0.43(0.24-0.79) for ever drinkers, 0.35(0.17-0.71) for low physical activity, 0.52(0.28-0.96) for hypertension, and 0.34(0.14-0.81) for dyslipidemia. Conclusions: A simple genetic score integrating the additive impact of eleven polymorphisms may identify those subjects at increased risk of CHD beyond conventional risk factors.