Pleiotropy-Based Decomposition of Genetic Risk Scores: Association and Interaction Analysis for Type 2 Diabetes and CAD.

ABSTRACT: Genetic risk for a disease in the population may be represented as a genetic risk score (GRS) constructed as the sum of inherited risk alleles, weighted by allelic effects established in an independent population. While this formulation captures overall genetic risk, it typically does not address risk due to specific biological mechanisms or pathways that may nevertheless be important for interpretation or treatment response. Here, a GRS for disease is resolved into independent or nearly independent components pertaining to biological mechanisms inferred from pleiotropic relationships. The component GRSs' weights are derived from the singular value decomposition (SVD) of the matrix of appropriately scaled genetic effects, i.e., beta coefficients, of the disease variants across a panel of t

SUBMITTER: Chasman DI 

PROVIDER: S-EPMC7212269 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature