Murine genetic association studies can identify genetic factors affecting a wide range of 21st century biomedical phenotypes. However, some alterations to the methodology, which was developed in the 20th century, is required to ensure that murine genetic association studies produce useful results. To facilitate genetic discovery, investigators should: 1) assess a phenotype across a large number (≥20) of inbred strains; 2) perform the genetic analysis using recently developed methods (such as ‘next generation’ HBCGM) that can optimally analyze the phenotypic data obtained from a large inbred strain panel; 3) use comprehensive genetic maps produced by analysis of whole genome sequencing data; and 4) integrate the analysis of the genetic association results with gene expression, metabolomic or other types of ‘omic’ datasets that are relevant to the phenotype. Next generation sequencing enables a genetic map covering a very large number of inbred strains to be assembled. Although not all biomedical traits can be analyzed by this approach, these four modifications should greatly increase the number of genetic discoveries that emerge from murine genetic association studies.
