Evidence map›Paper›PMID 38041181›Full record

ArticleArthritis research & therapy2023

Age-dependent genetic regulation of osteoarthritis: independent effects of immune system genes.

Jacob Kenny, Benjamin H Mullin, William Tomlinson, Brett Robertson, Jinbo Yuan, Weiwei Chen, Jinmin Zhao, Nathan J Pavlos, John P Walsh, Scott G Wilson and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arthritis research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.0field-weighted citation impact, top 12% of its field
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

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Article
  3. Methyltransferase-Like 3-Mediated NJournal of cellular and molecular medicine · 2025
    Review
  4. Article
  5. 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

13 authors at 6 institutions in 3 countries.

Jacob KennySchool of Biomedical Sciences, University of Western Australia, Crawley, WA, 6009, Australia. Jacob.kenny@uwa.edu.au.
Benjamin H MullinSchool of Biomedical Sciences, University of Western Australia, Crawley, WA, 6009, Australia.
William TomlinsonSchool of Biomedical Sciences, University of Western Australia, Crawley, WA, 6009, Australia.
Brett RobertsonAustralian Institute of Robotic Orthopaedics, Crawley, WA, Australia.
Jinbo YuanSchool of Biomedical Sciences, University of Western Australia, Crawley, WA, 6009, Australia.
Weiwei ChenResearch Centre for Regenerative Medicine, and Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China.
Jinmin ZhaoResearch Centre for Regenerative Medicine, and Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China.
Nathan J PavlosSchool of Biomedical Sciences, University of Western Australia, Crawley, WA, 6009, Australia.
John P WalshDepartment of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
Scott G WilsonSchool of Biomedical Sciences, University of Western Australia, Crawley, WA, 6009, Australia.
Jennifer TicknerSchool of Biomedical Sciences, University of Western Australia, Crawley, WA, 6009, Australia.
Grant Morahan *Centre for Diabetes Research, Harry Perkins Institute for Medical Research, Nedlands, WA, Australia. grant.morahan@perkins.org.au.
Jiake Xu *School of Biomedical Sciences, University of Western Australia, Crawley, WA, 6009, Australia.
University of Western Australia · AUSir Charles Gairdner Hospital · AUGuangxi Medical University · CNAustralian Centre for Robotic Vision · AUChinese Academy of Sciences · CNHarry Perkins Institute of Medical Research · AU

Funding

Australian National Health and Medical Research Council 1127156Australian National Health and Medical Research Council 2003629Department of Health, Government of Western Australia 1186046
6 · The paper itself

Abstract

objectivesOsteoarthritis (OA) is a joint disease with a heritable component. Genetic loci identified via genome-wide association studies (GWAS) account for an estimated 26.3% of the disease trait variance in humans. Currently, there is no method for predicting the onset or progression of OA. We describe the first use of the Collaborative Cross (CC), a powerful genetic resource, to investigate knee OA in mice, with follow-up targeted multi-omics analysis of homologous regions of the human genome.

methodsWe histologically screened 275 mice for knee OA and conducted quantitative trait locus (QTL) mapping in the complete cohort (> 8 months) and the younger onset sub-cohort (8-12 months). Multi-omic analysis of human genetic datasets was conducted to investigate significant loci.

resultsWe observed a range of OA phenotypes. QTL mapping identified a genome-wide significant locus on mouse chromosome 19 containing Glis3, the human equivalent of which has been identified as associated with OA in recent GWAS. Mapping the younger onset sub-cohort identified a genome-wide significant locus on chromosome 17. Multi-omic analysis of the homologous region of the human genome (6p21.32) indicated the presence of pleiotropic effects on the expression of the HLA - DPB2 gene and knee OA development risk, potentially mediated through the effects on DNA methylation.

conclusionsThe significant associations at the 6p21.32 locus in human datasets highlight the value of the CC model of spontaneous OA that we have developed and lend support for an immune role in the disease. Our results in mice also add to the accumulating evidence of a role for Glis3 in OA.

Indexed as

Genome-Wide Association StudyOsteoarthritis, KneeAnimalsGene Expression RegulationGenetic LociGenetic Predisposition to DiseaseHumansMicePhenotypeGeneticsGenome-wide associationImmune regulationOsteoarthritis

Identifiers

PMID38041181
PMCPMC10691153
OpenAlexW4389226695

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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 OpenQuestion graph.