Incremental predictive value of 152 single nucleotide polymorphisms in the 10-year risk prediction of incident coronary heart disease: The Rotterdam Study

Objective: To examine the incremental predictive value of genetic risk scores of coronary heart disease (CHD) in the 10-year risk prediction of incident CHD. Methods: In 5899 subjects, we used 152 single nucleotide polymorphisms (SNPs) associated with coronary artery disease by the CARDIoGRAMplusC4D consortium to construct three weighted genetic risk scores: (i) GRSgws based on 49 genome-wide significant SNPs; (ii) GRSfdr based on 103 suggestively associated SNPs; and (iii) GRSall based on all 152 SNPs. We examined the changes in discrimination and reclassification of incident CHD when adding the genetic risk scores to models including traditional risk factors. We repeated the analysis for prevalent CHD. Results: The genetic risk scores were associated with incident CHD despite adjustment for traditional risk factor