ArticleNature communications2025
Transcripts with high distal heritability mediate genetic effects on complex metabolic traits.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
7 citing papers in PubMed.
- Genetic architecture of the murine serum metabolome reveals carboxyl esterases as master regulators of circulating fatty acid metabolism.bioRxiv : the preprint server for biology · 2026Article
- Trans-regulation of heterochromatin underlies genetic variation in 3D genome contacts in mouse embryonic stem cells.Genome biology · 2026Article
- Distinct genetic architecture of gene and isoform level QTL in the Diversity Outbred (DO) mouse population.bioRxiv : the preprint server for biology · 2026Article
- Precision Nutrition in Type 2 Diabetes Prevention Through Molecular Nutrigenomic and Epigenetic Modulation of Insulin Signaling and Glucose Metabolism.International journal of molecular sciences · 2026Review
- Fifteen years of the Diversity Outbred mouse model: a review.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Identifying transcriptomic signatures that mediate the causal effect of genotype on Alzheimer's disease.Frontiers in neuroscience · 2026Article
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Abstract
Although many genes are subject to local regulation, recent evidence suggests that complex distal regulation may be more important in mediating phenotypic variability. To assess the role of distal gene regulation in complex traits, we combine multi-tissue transcriptomes with physiological outcomes to model diet-induced obesity and metabolic disease in a population of Diversity Outbred mice. Using a novel high-dimensional mediation analysis, we identify a composite transcriptome signature that summarizes genetic effects on gene expression and explains 30% of the variation across all metabolic traits. The signature is heritable, interpretable in biological terms, and predicts obesity status from gene expression in an independently derived mouse cohort and multiple human studies. Transcripts contributing most strongly to this composite mediator frequently have complex, distal regulation distributed throughout the genome. These results suggest that trait-relevant variation in transcription is largely distally regulated, but is nonetheless identifiable, interpretable, and translatable across species.
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