Evidence map›Paper›PMID 42730883›Full record

ArticleJournal of molecular neuroscience : MN2026

Mitochondrial Function-Related Genes in Sleep Disorders: A Multi-Omics Mendelian Randomization Study.

Junjun Xu, Ziyan Zhang, Liuyang Yu, Yi Feng

Abstract read
In one paragraph

Article in Journal of molecular neuroscience : MN, 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

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Junjun XuDepartment of Anesthesiology, Peking University People's Hospital, Beijing, 100044, China.
Ziyan ZhangDepartment of Anesthesiology, Peking University People's Hospital, Beijing, 100044, China.
Liuyang YuDepartment of Anesthesiology, Peking University People's Hospital, Beijing, 100044, China.
Yi FengDepartment of Anesthesiology, Peking University People's Hospital, Beijing, 100044, China. doc_yifeng@163.com.ORCID http://orcid.org/0000-0002-3952-1351

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mitochondrial dysfunction is linked to sleep disorders in previous report, but the potential roles of specific genes remain unclear. This study aimed to dissect different subtype-specific genetic associations and their underlying mechanisms. A multi-omics Summary-data-based Mendelian Randomization (SMR) approach was performed to identify potential causal links between mitochondrial function-related genes and sleep disorders. We integrated GWAS data from FinnGen database (the discovery set), independent GWAS datasets (covering different sleep-disorder subtypes and used for validation), and cis-QTLs (including mQTLs, eQTLs, and pQTLs) to perform systematic exploration. Specially, we performed targeted validation of tissue-specific effects, leveraging gene expression data from disease-relevant brain regions within the GTEx database. Our SMR analysis identified mitochondrial function-related genes potentially modulating sleep disorders across biological layers, initially identifying 102 genes at the methylation level, 48 at the gene expression level, and 6 at the protein abundance level. Integrative analysis subsequently prioritized DCXR and ACADVL and revealed their distinct, subtype-specific associations. DCXR exhibited a protective role in sleep apnea while ACADVL showed a paradoxical risk conferring role in daytime sleepiness. In addition, the analysis identified an epigenetic regulatory mechanism for DCXR in which its expression and protein levels are modulated by DNA methylation. Finally, validation in brain-hypothalamus tissue confirmed DCXR as a significant potential protective factor (OR = 0.929, 95% CI: 0.887-0.973, P_HEIDI = 0.999, FDR = 0.2449). Our findings implicate key mitochondrial genes, particularly DCXR and ACADVL, in the pathophysiology of specific sleep disorder subtypes, highlighting potential avenues for precision medicine. Clinical trial number: Not applicable.

Indexed as

MitochondriaSleep Wake DisordersGenome-Wide Association StudyHumansMendelian Randomization AnalysisMultiomicsQuantitative Trait LociMendelian randomization analysisMitochondrial functionMulti-omicsSleep disorders

Identifiers

PMID42730883
PMCPMC13570829

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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.