Pharmacological enrichment of polygenic risk for precision medicine in complex disorders.

ABSTRACT: Individuals with complex disorders typically have a heritable burden of common variation that can be expressed as a polygenic risk score (PRS). While PRS has some predictive utility, it lacks the molecular specificity to be directly informative for clinical interventions. We therefore sought to develop a framework to quantify an individual's common variant enrichment in clinically actionable systems responsive to existing drugs. This was achieved with a metric designated the pharmagenic enrichment score (PES), which we demonstrate for individual SNP profiles in a cohort of cases with schizophrenia. A large proportion of these had elevated PES in one or more of eight clinically actionable gene-sets enriched with schizophrenia associated common variation. Notable candidates targeting these p

SUBMITTER: Reay WR 

PROVIDER: S-EPMC6972917 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature