Evidence map›Paper›PMID 42071838›Full record

ArticleMedicine2026

DNA methylation-regulated ZDHHC5 and PPT1 in the pathogenesis of osteoporosis.

Chao Wang, Yong Zhu, Zhe Ruan

Abstract read
In one paragraph

Article in Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

Who cites it

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4 · The record

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5 · Who and what money

Authors and funding

3 authors.

Chao WangDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
Yong ZhuDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
Zhe RuanDepartment of Orthopaedics, The First Hospital of Changsha, Changsha, Hunan Province, China.ORCID 0000-0002-6714-6069

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

While osteoporosis (OP) affects over 200 million people globally, the causal roles of protein palmitoylation and its upstream epigenetic regulation in the pathogenesis of the disease remain undefined. We aimed to investigate whether DNA methylation causally influences OP risk by modulating the expression of palmitoylation-related genes. We employed an integrated multi-omics causal inference framework, combining 2-sample Mendelian randomization (MR), summary-data-based MR, Bayesian colocalization, and 2-step mediation MR analyses. Data were sourced from large-scale consortia: the FinnGen study (genome-wide association study: 10,461 cases, 473,264 controls), eQTLGen, GTEx (expression quantitative trait loci), and the GoDMC database (methylation quantitative trait loci). Two-sample MR identified ZDHHC5 as a protective factor (odds ratio = 0.81, 95% confidence interval: 0.76-0.87; P = 6.8 × 10-9) and the depalmitoylase PPT1 as a risk factor (odds ratio = 1.06, 95% confidence interval: 1.03-1.08; P = 7.9 × 10-5) for OP. These findings were corroborated by summary-data-based analysis, and colocalization confirmed a shared causal variant at the ZDHHC5 locus (posterior probability of H4 = 0.947). Mediation analysis revealed that DNA methylation is a central mechanistic link: methylation at site cg13473383 mediated 92.7% of ZDHHC5's protective effect, while sites cg04560534 and cg07033722 mediated 74.8% and 43.4%, respectively, of PPT1's risk effect. This study is the first to establish a causal epigenetic-palmitoylation axis in OP. The genes ZDHHC5 and PPT1, regulated by specific DNA methylation sites, represent novel potential therapeutic targets and biomarkers, offering fresh insights for precision medicine strategies against bone loss.

Indexed as

AcyltransferasesDNA MethylationOsteoporosisThiolester HydrolasesEpigenesis, GeneticGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansLipoylationMendelian Randomization AnalysisPolymorphism, Single NucleotideQuantitative Trait LociAcyltransferasespalmitoyl-protein thioesteraseThiolester HydrolasesDNA methylationepigenetic regulationMendelian randomizationosteoporosispalmitoylation

Identifiers

PMID42071838
PMCPMC13124397

What Socratic holds

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LicenceCC BY
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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.