Power and precision: Evaluation and recommendations of quantitative trait analysis methods for RNA expression levels in the Hybrid Rat Diversity Panel

Abstract

The Hybrid Rat Diversity Panel (HRDP) is a stable and well-characterized set of more than 90 inbred rat strains that can be leveraged for systems genetics approaches to understanding the genetic and genomic variation associated with complex disease. The HRDP exhibits substantial between-strain diversity while retaining substantial within-strain isogenicity, allowing for the precise mapping of genetic variation associated with complex phenotypes and providing statistical power to identify associated variants. In order to robustly identify associated genetic variants, it is important to account for the population structure induced by inbreeding. To this end, we investigate the performance of various plausible approaches towards modeling quantitative traits in the HRDP and quantify their operating characteristics. Towards facilitating study planning and design, we conduct extensive simulations to investigate the power of genetic association analyses in the HRDP, and characterize the impressive attained power.