| Title: | Systems genetics of metabolic health in the BXD mouse genetic reference population |
| Journal: | Cell Systems |
| Published: | 11 Jun 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38866010/ |
| DOI: | https://doi.org/10.1016/j.cels.2024.05.006 |
| URL: | http://www.cell.com/article/S2405471224001509/pdf |
Publication 11880
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Abstract
Susceptibility to metabolic syndrome (MetS) is dependent on genetics, environment, and gene-by-environment interactions, rendering the study of underlying mechanisms challenging. The majority of experiments in model organisms do not incorporate genetic variation and lack specific evaluation criteria for MetS. Here, we derived a continuous metric, the metabolic health score (MHS), based on standard clinical parameters and defined its molecular signatures in the liver and circulation. In human UK Biobank, the MHS associated with MetS status and was predictive of future disease incidence, even in individuals without MetS. Using quantitative trait locus analyses in mice, we found two MHS-associated genetic loci and replicated them in unrelated mouse populations. Through a prioritization scheme in mice and human genetic data, we identified TNKS and MCPH1 as candidates mediating differences in the MHS. Our findings provide insights into the molecular mechanisms sustaining metabolic health across species and uncover likely regulators. A record of this paper's transparent peer review process is included in the supplemental information.</p>
11 Keywords
- Animals
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Male
- Metabolic Syndrome
- Mice
- Mice, Inbred C57BL
- Quantitative Trait Loci
- Systems Biology
12 Authors
- Xiaoxu Li
- Jean-David Morel
- Jonathan Sulc
- Alessia De Masi
- Amélia Lalou
- Giorgia Benegiamo
- Johanne Poisson
- Yasmine Liu
- Giacomo V G Von Alvensleben
- Arwen W Gao
- Maroun Bou Sleiman
- Johan Auwerx
1 Application
| Application ID | Title |
|---|---|
| 48020 | Exploring Diet/Lifestyle/Health factors as causes and modifiers of genetic determinants of healthspan, ageing and longevity |
Enabling scientific discoveries that improve human health