Evidence map›Paper›PMID 40480217›Full record

ArticleCell genomics2025

Extensive differential gene expression and regulation by sex in human skeletal muscle.

Sarah C Hanks, Abigail S Mauger, Arushi Varshney, Dan L Ciotlos, Nandini Manickam, Narisu Narisu, Alexandria J Shumway, Peter Orchard, Michael R Erdos, Michael D Sweeney and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
–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

9 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Oleic Acid Levels in HSAInternational journal of molecular sciences · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. The Long Non-coding RNA Landscape of Endurance Exercise Training.bioRxiv : the preprint server for biology · 2025
    Article
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

25 authors.

Sarah C HanksDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Abigail S MaugerDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Arushi VarshneyDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
Dan L CiotlosDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Nandini ManickamDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
Narisu NarisuCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Alexandria J ShumwayDepartment of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA.
Peter OrchardDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
Michael R ErdosCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Michael D SweeneyDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Jeffrey OkamotoDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Anne U JacksonDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Heather M StringhamDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Lori L BonnycastleCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Xiang ZhouDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Timo A LakkaInstitute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, Finland; Kuopio Research Institute of Exercise Medicine, Kuopio, Finland; Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
Karen L MohlkeDepartment of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
Jaakko TuomilehtoDepartment of Public Health, Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Public Health, University of Helsinki, Helsinki, Finland; Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
Markku LaaksoInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
Michael BoehnkeDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Praveen SethupathyDepartment of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA.
Francis S CollinsCenter for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Heikki A KoistinenDepartment of Public Health, Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland.
Stephen C J ParkerDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
Laura J ScottDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: ljst@umich.edu.

Funding

Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAVID P OLSON · 2013 to 2026
$24.3M
University of Michigan Training Program in Genomic ScienceT32HG000040 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sebastian Zoellner · 1995 to 2026
$16.4M
Identifying Genes for Type 2 Diabetes:FUSIONR01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2003 to 2025
$6.7M
NHGRI NIH HHS T32 HG000040NIDDK NIH HHS P30 DK020572NIDDK NIH HHS R01 DK062370
6 · The paper itself

Abstract

The identification of sex-differential gene regulatory elements is essential for understanding sex-differential patterns of health and disease. We leveraged bulk and single-nucleus RNA sequencing (RNA-seq) and single-nucleus ATAC-seq data from 281 skeletal muscle biopsies to characterize sex differences in gene expression and regulation at the cell-type and whole-tissue levels. We found highly concordant sex-biased expression of over 2,100 genes across the three muscle fiber types and bulk tissue. Gene pathways related to mitochondrial activity and energy metabolism were enriched for male-biased expression, whereas those related to signal transduction and cell differentiation were enriched for female-biased expression. We found widespread sex-biased chromatin accessibility enriched in proximal and distal gene regulatory states; in gene promoters, sex-biased chromatin accessibility was positively associated with sex-biased expression. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) also showed extensive sex-biased expression in the fiber-type and bulk data, respectively. Together, these results highlight nuclear and cytoplasmic mechanisms for sex-differential gene regulation in skeletal muscle.

Indexed as

Gene Expression RegulationMuscle, SkeletalChromatinFemaleHumansMaleMicroRNAsRNA, Long NoncodingSex CharacteristicsSex FactorsChromatinMicroRNAsRNA, Long Noncodingchromatin accessibilitygene expressiongene regulationmiRNAsex differencessingle nucleusskeletal musclesnATAC-seqsnRNA-seq

Identifiers

PMID40480217
PMCPMC12366654

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.