Distinct genetic liability profiles define clinically relevant patient strata across common diseases.

ABSTRACT: Genome-wide association studies have unearthed a wealth of genetic associations across many complex diseases. However, translating these associations into biological mechanisms contributing to disease etiology and heterogeneity has been challenging. Here, we hypothesize that the effects of disease-associated genetic variants converge onto distinct cell type specific molecular pathways within distinct subgroups of patients. In order to test this hypothesis, we develop the CASTom-iGEx pipeline to operationalize individual level genotype data to interpret personal polygenic risk and identify the genetic basis of clinical heterogeneity. The paradigmatic application of this approach to coronary artery disease and schizophrenia reveals a convergence of disease associated variant effects onto kno

SUBMITTER: Trastulla L 

PROVIDER: S-EPMC10197798 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature