Alanna C. Morrison

Abstract Polygenic risk score values vary with genetic ancestry due to differences in population-specific allele frequencies and linkage disequilibrium patterns. We present a framework to calibrate polygenic risk scores based on ancestral makeup. We propose the “expected polygenic risk score” or ePRS, defined as the expected value of a polygenic risk score based on one’s global or local admixture patterns.

Abstract Multiple germline and somatic genomic factors are associated with risk of coronary artery disease, but there is no single measure of risk that integrates all information from a DNA sample. To address this gap, we develop an integrated genomic model that includes six germline and somatic genetic drivers for coronary artery disease, including polygenic risk score, genetically-proxied proteomic/metabolomic risk scores, and clonal hematopoiesis of indeterminate potential.

MKG conceived the study, analyzed the data of the UK Biobank, performed the meta-analyses for the M249K variant, supervised this work, drafted the first version of the manuscript and reviewed the manuscript for intellectual content. RM performed the burden test analyses and phenome-wide association study in the UK Biobank, drafted the first version of the manuscript and reviewed the manuscript for intellectual content.