Evidence map›Paper›PMID 40877285›Full record

ArticleScientific reports2025

Identification and replication of sex-dimorphic protein quantitative trait loci across multiple ancestries and their associations with diseases.

Youngjune Bhak, Vasilis Raptis, Yunye He, Tomoko Nakanishi, Erin Macdonald-Dunlop, Yoji Sagiya, Takayuki Morisaki, Koichi Matsuda, BioBank Japan Project, Japan COVID-19 Task Force and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

26 authors.

Youngjune Bhak *The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, UK. youngjune29bhak@gmail.com.
Vasilis Raptis *The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, UK.
Yunye HeLaboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
Tomoko NakanishiDepartment of Genome Informatics, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Erin Macdonald-DunlopDepartment of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
Yoji SagiyaThe University of Tokyo, Tokyo, Japan.
Takayuki MorisakiThe University of Tokyo, Tokyo, Japan.
Koichi MatsudaThe University of Tokyo, Tokyo, Japan.
BioBank Japan Project
Japan COVID-19 Task Force
Akinori KanaiLaboratory of Systems Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
Yutaka SuzukiLaboratory of Systems Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
Yoshiya OdaDepartment of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yoichiro KamataniLaboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
Ho NamkoongDepartment of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan.
Ryunosuke SaikiDepartment of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan.
Akinori KimuraInstitute of Science, Tokyo, Japan.
Ryuji KoikeMedical Innovation Promotion Center, Tokyo Medical and Dental University, Tokyo, Japan.
Seishi OgawaDepartment of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan.
Satoru MiyanoM&D Data Science Center, Institute of Science, IIR, Tokyo, Japan.
Seiya ImotoDivision of Health Medical Intelligence, Human Genome Center, the Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Takanori KanaiDivision of Gastroenterology and Hepatology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Koichi FukunagaDivision of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Yukinori OkadaDepartment of Genome Informatics, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Anders MälarstigDepartment of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. anders.malarstig@ki.se.
Albert TenesaThe Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, UK. Albert.Tenesa@ed.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Males and females exhibit differences in proteome profiles associated with disease risk. However, sex-dimorphic protein quantitative trait loci (SD-pQTL) and their effects on sex differences in health disorders have not been thoroughly investigated. We conducted a sex-stratified, genome-wide association study on 2,922 proteins using data from 30,272 individuals of Caucasian ancestry from the UK Biobank and compared the estimated effects on protein levels of these variants in the men and women to identify SD-pQTLs. The identified SD-pQTLs were replicated using data from two Japanese cohorts (comprising 2,886 and 1,394 individuals, respectively), as well as from 1,990 Finnish, 630 South Asian, and 662 Black ancestry individuals. Sex-dimorphic pleiotropy and the causal relationship between protein levels and health disorders were assessed using the identified SD-pQTLs. We identified 113 SD-pQTLs associated with 65 proteins. Of the 113 SD-pQTLs, 52 were significant in both sexes, five were not significant in either sex, and 42 and 14 were significant only in males and females, respectively. Variant rs2270416 was significantly associated with the CDH15 protein in both sexes but showed opposite effect direction in men and women. Of the 113 SD-pQTLs identified, a total of 41 were replicated in a meta-analysis encompassing Japanese, South Asian, and Black ancestry individuals. SD-pQTLs for proteins APOE (rs157581) and SNAP25 (rs4420638) exhibited sex-dimorphic associations with dementia, indicating sex dimorphic pleiotropy in both proteins and health disorders. From sex-stratified Mendelian randomization using the SD-pQTLs, proteins NCAM1 and PZP showed significant causal relationship with dementia in males and females, respectively. The present study provides evidence of sex-dimorphic genetic architecture in protein-level regulation, elucidating the proteo-genetic architecture for sex differences in human variation.

Indexed as

Genetic Predisposition to DiseaseQuantitative Trait LociSex CharacteristicsAsian PeopleFemaleGenome-Wide Association StudyHumansMalePolymorphism, Single NucleotideWhite PeopleProteome profilesSex differencesSex-dimorphic protein quantitative trait loci

Identifiers

PMID40877285
PMCPMC12394655

What Socratic holds

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Registered trials

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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.