A composite scoring of genotypes discriminates coronary heart disease risk beyond conventional risk factors in the Boston Puerto Rican Health Study

Abstract 

Background and aims

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 and results

We studied 11 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 1unit (high-risk allele homozygous), 0.5units (heterozygous) and 0units (low-risk allele homozygous) to the GPS. Odds ratio (OR) of CHD for those at high risk because of GPS (>5) and simultaneous presence of CRFs were estimated, compared with subjects at low risk, for both measurements.

The mean score was higher in participants with prior CHD than those CHD-free (P=0.015), and the OR for CHD with a GPS>5 was 2.90 (P<0.001).The joint presence of a high GPS and each CRF was associated with higher risk of CHD. Compared to participants with high GPS, those with low GPS (≤5) were protected against CHD even if they were smokers (OR=0.44), heavy drinkers (OR=0.43), displayed low physical activity (OR=0.35), had hypertension (OR=0.52) or hyperlipidemia (OR=0.34) (P values ranging from 0.004 to 0.023).

Conclusion

A simple genetic score of 11 polymorphisms may identify those subjects at increased risk of CHD beyond conventional risk factors.

Keywords: Genes, Coronary heart disease, Conventional risk factors, Genetic predisposition score, Single nucleotide polymorphism