Evidence map›Paper›PMID 41256396›Full record

ArticlebioRxiv : the preprint server for biology2025

Integrative multi-omics uncovers skeletal muscle enhancer programming of cardiorespiratory fitness.

Anne M Weitzel, Peter Orchard, Charles R Evans, Nandini Manickam, Mary K Treutelaar, Steven L Britton, Lauren Koch, Jun Z Li, Stephen C J Parker, Charles F Burant

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Anne M WeitzelMolecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-7615-6357
Peter OrchardComputational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-6097-1106
Charles R EvansInternal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-6698-5330
Nandini ManickamComputational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-9809-9712
Mary K TreutelaarInternal Medicine, University of Michigan, Ann Arbor, MI, USA.
Steven L BrittonMolecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Lauren KochPhysiology & Pharmacology, The University of Toledo, Toledo, Ohio, USA.
Jun Z LiMolecular Genetics and Genome Sciences, The University of Oklahoma Health Campus, Oklahoma City, OK, USA.ORCID 0000-0001-6727-0812
Stephen C J ParkerComputational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
Charles F BurantMolecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-9189-5003

Funding

Pilot and Feasibility (P and F) ProgramP30DK089503 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Joyce Lee · 2010 to 2026
$20.3M
Michigan MoTrPAC Chemical Analysis Site (MiCAS)U24DK112342 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHARLES F BURANT, CHARLES ROBERT EVANS · 2017 to 2026
$12.6M
SYTEMS AND INTEGRATIVE BIOLOGYT32GM008322 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LOW, MALCOLM JAMES · 1990 to 2020
$5.7M
Context-specific and combinatorial genetic regulatory grammars in diabetesR01DK117960 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Stephen CJ Parker · 2018 to 2026
$2.8M
NIDDK NIH HHS P30 DK089503NIDDK NIH HHS R01 DK117960NIDDK NIH HHS U24 DK112342NIGMS NIH HHS T32 GM008322
6 · The paper itself

Abstract

Cardiorespiratory fitness (CRF) is a heritable trait associated with improved metabolic health and reduced mortality. To identify regulatory mechanisms associated with CRF variation, we generated and integrated 546 transcriptomic and epigenomic (chromatin accessibility and histone marks) profiles from 128 genetically heterogeneous rats selectively bred for high and low running capacity, a model that mirrors CRF-associated traits in humans. We found that selection for high CRF led to genetic convergence in skeletal muscle regulatory regions linked to genes involved in lipid metabolism and angiogenesis. We validated thousands of these genetic effects through generation and integration of 426 genotype, gene expression, and chromatin accessibility profiles in an independent HCR×LCR F2 population (n=147). Together, these 972 omics profiles show that genetic variation reshapes the chromatin landscape to support energy metabolism and oxygen delivery in skeletal muscle and overall CRF, offering a molecular framework to identify targets that reduce cardiometabolic disease risk.

Identifiers

PMID41256396
PMCPMC12621784

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.