BACKGROUND: Numerous risk prediction algorithms based on conventional risk factors for @entity301 ( @entity301 ) are available but provide only modest discrimination. The inclusion of genetic information may improve clinical utility. METHODS: We tested the use of two @entity74 ( @entity74 ) in the prospective second Northwick Park Heart Study (NPHSII) of 2775 healthy UK @entity1 (284 cases), and Pakistani case-control studies from Islamabad/Rawalpindi (321 cases/228 controls) and Lahore (414 cases/219 controls). The 19-SNP @entity74 included SNPs in loci identified by GWAS and candidate gene studies, while the 13-SNP @entity74 only included SNPs in loci identified by the CARDIoGRAMplusC4D consortium. RESULTS: In NPHSII, the mean of both @entity74 was higher in those who went on to develop @entity301 over 13.5 years of follow-up (19-SNP p=0.01, 13-SNP p=7x10-3). In combination with the Framingham algorithm the GSs appeared to show improvement in discrimination (increase in area under the ROC curve, 19-SNP p=0.48, 13-SNP p=0.82) and risk classification (net reclassification improvement (NRI), 19-SNP p=0.28, 13-SNP p=0.42) compared to the Framingham algorithm alone, but these were not statistically significant. When considering only individuals who moved up a risk category with inclusion of the @entity74 , the improvement in risk classification was statistically significant (19-SNP p=0.01, 13-SNP p=0.04). In the Pakistani samples, risk allele frequencies were significantly lower compared to NPHSII for 13/19 SNPs. In the Islamabad study, the mean gene score was higher in cases than controls only for the 13-SNP @entity74 (2.24 v 2.34, p=0.04). There was no association with @entity301 and either score in the Lahore study. CONCLUSION: The performance of both GSs showed potential clinical utility in European @entity1 but much less utility in subjects from Pakistan, suggesting that a different set of risk loci or SNPs may be required for risk prediction in the South Asian population.

Clinical Utility of a XXXX Risk Prediction Gene Score in UK Healthy Middle Aged @entity1 and in the Pakistani Population.

@entity1 :: ('9606', 'Species') :: ['men'] @entity74 :: ('MESH:D030342', 'Disease') :: ['gene scores', 'GS'] @entity301 :: ('MESH:D003327', 'Disease') :: ['CHD', 'Coronary Heart Disease']
@entity301 :: (MESH:D003327,Disease) :: ['Coronary Heart Disease']
