Association of Genetically Predicted Levels of Circulating Blood Lipids with Coronary Artery Disease Incidence

Abstract

BackgroundEstimating the genetic risk of coronary artery disease (CAD) is now possible by aggregating data from genome-wide association studies (GWAS) into polygenic risk scores (PRS). Combining multiple PRS for specific circulating blood lipids could improve risk prediction. Here, we sought to evaluate the performance of PRS derived from CAD and blood lipids GWAS to predict the incidence of CAD. MethodsThis study included individuals aged between 40 and 69 recruited in UK Biobank (UKB). We conducted GWAS for blood lipids measured by nuclear magnetic resonance in individuals without lipid-lowering treatments (n=73,915). Summary statistics were used to derive and calculate PRS in the remaining participants (n=318,051). A PRSCAD was also derived using the CARDIoGRAMplusC4D GWAS. Hazard ratios (HR) for CAD (9,017 / 301,576; median follow-up time: 12.6 years) were calculated per standard deviation increase in each PRS. Discrimination capacity and goodness of fit of the models were evaluated. ResultsOut of 30 PRS, 28 were significantly associated with the incidence of CAD (P View larger version (54K): org.highwire.dtl.DTLVardef@113a499org.highwire.dtl.DTLVardef@9b79fcorg.highwire.dtl.DTLVardef@165c1f7org.highwire.dtl.DTLVardef@1a166d3_HPS_FORMAT_FIGEXP M_FIG C_FIG