The potential of integrating human and mouse discovery platforms to advance our understanding of cardiometabolic diseases
Open Access
- 31 March 2023
- journal article
- review article
- Published by eLife Sciences Publications, Ltd in eLife
Abstract
Cardiometabolic diseases encompass a range of interrelated conditions that arise from underlying metabolic perturbations precipitated by genetic, environmental, and lifestyle factors. While obesity, dyslipidaemia, smoking, and insulin resistance are major risk factors for cardiometabolic diseases, individuals still present in the absence of such traditional risk factors, making it difficult to determine those at greatest risk of disease. Thus, it is crucial to elucidate the genetic, environmental, and molecular underpinnings to better understand, diagnose, and treat cardiometabolic diseases. Much of this information can be garnered using systems genetics, which takes population-based approaches to investigate how genetic variance contributes to complex traits. Despite the important advances made by human genome-wide association studies (GWAS) in this space, corroboration of these findings has been hampered by limitations including the inability to control environmental influence, limited access to pertinent metabolic tissues, and often, poor classification of diseases or phenotypes. A complementary approach to human GWAS is the utilisation of model systems such as genetically diverse mouse panels to study natural genetic and phenotypic variation in a controlled environment. Here, we review mouse genetic reference panels and the opportunities they provide for the study of cardiometabolic diseases and related traits. We discuss how the post-GWAS era has prompted a shift in focus from discovery of novel genetic variants to understanding gene function. Finally, we highlight key advantages and challenges of integrating complementary genetic and multi-omics data from human and mouse populations to advance biological discovery.This publication has 220 references indexed in Scilit:
- Large-scale association analysis identifies new risk loci for coronary artery diseaseNature Genetics, 2012
- Hybrid mouse diversity panel: a panel of inbred mouse strains suitable for analysis of complex genetic traitsMammalian Genome, 2012
- The Drosophila melanogaster Genetic Reference PanelNature, 2012
- Large-scale association analysis identifies 13 new susceptibility loci for coronary artery diseaseNature Genetics, 2011
- Replication of past candidate loci for common diseases and phenotypes in 100 genome-wide association studiesEuropean Journal of Human Genetics, 2010
- Design of aging intervention studies: the NIA interventions testing programAGE, 2008
- Variations in DNA elucidate molecular networks that cause diseaseNature, 2008
- The polymorphism architecture of mouse genetic resources elucidated using genome-wide resequencing data: implications for QTL discovery and systems geneticsMammalian Genome, 2007
- The Collaborative Cross, a community resource for the genetic analysis of complex traitsNature Genetics, 2004
- Initial sequencing and comparative analysis of the mouse genomeNature, 2002