Evidence map›Paper›PMID 41028716›Full record

ArticleNature communications2025

Concordance between male- and female-specific GWAS results helps define underlying genetic architecture of complex traits.

Anna K Miller, Jacquelaine Bartlett, Calvin Pan, Aldons J Lusis, Dana C Crawford, Scott M Williams, David A Buchner

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

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 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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

7 authors.

Anna K MillerDepartment of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Jacquelaine BartlettDepartment of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Calvin PanDepartments of Medicine, Microbiology, and Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Aldons J LusisDepartments of Medicine, Microbiology, and Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-9013-0228
Dana C CrawfordDepartment of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.ORCID http://orcid.org/0000-0002-6437-6248
Scott M Williams *Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA. smw154@case.edu.ORCID http://orcid.org/0000-0002-4835-9544
David A Buchner *Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA. dab22@case.edu.ORCID http://orcid.org/0000-0003-3920-4871

Funding

Role of adipocyte gene expression regulation by Zfp407 in adipocyte biology and metabolic diseaseR01DK119305 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI BUCHNER, DAVID A · 2019 to 2023
$2.0M
NIDDK NIH HHS R01 DK119305U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) 5T32HL007567-35U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK119305U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM) LM010098
6 · The paper itself

Abstract

A better understanding of genetic architecture will help enhance precision medicine and clinical care. Towards this end, we investigate sex-stratified analyses for several traits in the Hybrid Mouse Diversity Panel (HMDP) and UK Biobank to assess trait polygenicity and identify contributing loci. By comparing allelic effect directions in males and females, we hypothesize that non-associated loci should show random effect directions across sexes. Instead, we observe strong concordance in effect direction, even among alleles lacking nominal statistical significance. Our findings suggest hundreds of loci influence each mouse trait and thousands affect each human trait, including traits with no significant loci under conventional approaches. We also detect patterns consistent with spurious widespread epistasis. These results highlight the value of sex-stratified analyses in uncovering novel loci, suggest a method for identifying biologically relevant associations beyond statistical thresholds, and caution that pervasive main effects may produce misleading epistatic signals.

Indexed as

Genome-Wide Association StudyMultifactorial InheritanceAllelesAnimalsEpistasis, GeneticFemaleHumansMaleMicePhenotypePolymorphism, Single NucleotideQuantitative Trait LociSex Factors

Identifiers

PMID41028716
PMCPMC12485208

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.