Evidence map›Paper›PMID 40307428›Full record

ArticleMolecular neurobiology2025

Mitochondrial DNA Copy Number as a Hidden Player in the Progression of Multiple Sclerosis: A Bidirectional Two-Sample Mendelian Randomization Study.

Hani Sabaie, Ali Taghavi Rad, Motahareh Shabestari, Danial Habibi, Toktam Saadattalab, Sahar Seddiq, Amir Hossein Saeidian, Asiyeh Sadat Zahedi, Maryam Sanoie, Hassan Vahidnezhad and 7 more

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Article in Molecular neurobiology, 2025. 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

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4 · The record

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5 · Who and what money

Authors and funding

17 authors.

Hani Sabaie *Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Ali Taghavi Rad *Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Motahareh ShabestariYazd Cardiovascular Research Center, Non-Communicable Diseases Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Danial HabibiDepartment of Epidemiology and Biostatistics, School of Public Health, Babol University of Medical Sciences, Babol, Iran.
Toktam SaadattalabDepartment of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Sahar SeddiqOsteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Amir Hossein SaeidianCenter for Applied Genomics (CAG), The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Asiyeh Sadat ZahediCellular and Molecular Endocrine Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Maryam SanoieCellular and Molecular Endocrine Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Hassan VahidnezhadCenter for Applied Genomics (CAG), The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Maryam ZarkeshCellular and Molecular Endocrine Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Laleh ForoutaniDepartment of Surgery, University of California, San Francisco, CA, USA.
Hakon HakonarsonCenter for Applied Genomics (CAG), The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Fereidoun AziziEndocrine Research Center, Research Institute for Endocrine Disorders, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Mehdi HedayatiCellular and Molecular Endocrine Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Maryam Sadat DaneshpourCellular and Molecular Endocrine Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. daneshpour@sbmu.ac.ir.
Mahdi AkbarzadehCellular and Molecular Endocrine Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. akbarzadeh.ms@gmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The relationship between mitochondrial DNA copy number (mtDNA-CN) and multiple sclerosis (MS) progression remains unclear, as previous observational studies have reported conflicting results. This study aimed to clarify the association between mtDNA-CN and MS progression using a bidirectional two-sample Mendelian randomization (MR) approach. MR analyses were conducted using the latest summary statistics from genome-wide association studies (GWAS) on mtDNA-CN and MS progression. Single-nucleotide polymorphisms (SNPs) associated with mtDNA-CN were extracted from 383,476 participants of European ancestry in the UK Biobank, while SNPs associated with MS severity were obtained from the International Multiple Sclerosis Genetics Consortium (IMSGC), comprising 12,584 cases of European ancestry. The inverse variance weighted (IVW) method was used as the primary analysis. Potential heterogeneity and pleiotropy were evaluated, and sensitivity analyses were performed to ensure the robustness of the results. The forward MR analysis using the IVW method revealed no significant association between mtDNA-CN and MS progression (P = 0.487). However, reverse MR analysis identified a causal association between MS progression and mtDNA-CN (β =  - 0.010, 95% CI =  - 0.019 to - 0.001, P = 0.036). No evidence of heterogeneity or horizontal pleiotropy was found in the analyses. Sensitivity analyses yielded consistent results. Our findings suggest that MS progression may causally influence mtDNA-CN, highlighting the crucial role of mitochondria in the pathophysiology of MS. However, further research is needed to confirm mtDNA-CN as a reliable biomarker and a deeper understanding of the molecular mechanisms is necessary to develop targeted therapeutic interventions.

Indexed as

Disease ProgressionDNA Copy Number VariationsDNA, MitochondrialMendelian Randomization AnalysisMultiple SclerosisFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMalePolymorphism, Single NucleotideDNA, MitochondrialBidirectionalGenome-wide association studiesMendelian randomizationMitochondrial DNA copy numberMultiple sclerosis

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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.