Evidence map›Paper›PMID 39831399›Full record

ArticleBrain and behavior2025

Bidirectional Mendelian Randomization Analysis of the Association Between Mitochondrial Proteins and Neurodegenerative Diseases.

Fangyuan Wang, Zhou Jing, Qingyi Wang, Minghe Li, Bingqi Lu, Ao Huo, Chenglin Zhao, Huanyu Zhou, Wulong Liang, Weihua Hu and 1 more

Abstract read
In one paragraph

Article in Brain and behavior, 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
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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

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Integrating causal human genetics andFrontiers in molecular biosciences · 2025
    Article
4 · The record

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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

11 authors.

Fangyuan WangDepartment of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.ORCID https://orcid.org/0009-0000-8952-5441
Zhou JingDepartment of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Qingyi WangDepartment of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Minghe LiDepartment of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Bingqi LuDepartment of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Ao HuoDepartment of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Chenglin ZhaoDepartment of Clinical Medicine, The First Clinical Medical College of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Huanyu ZhouDepartment of Clinical Medicine, The First Clinical Medical College of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Wulong LiangDepartment of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Weihua HuDepartment of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Xudong FuDepartment of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.

Funding

Health Commission of Henan Province YXKC2022020National Natural Science Foundation of China 82303029Science and Technology Department of Henan Province 232102311134the Zhengzhou Science and Technology Innovation Project for Healthcare 2024YLZDJH027
6 · The paper itself

Abstract

backgroundNeurodegenerative diseases involve progressive neuronal dysfunction and cognitive decline, posing substantial global challenges. Although the precise causes remain unclear, several studies highlight the role of protein metabolism abnormalities in disease development. This study investigates the causal links between variations in mitochondrial protein genes and neurodegenerative diseases, aiming to elucidate their potential contributions to disease progression and identify novel therapeutic strategies.

methodsHerein, we utilized data from genome-wide association studies (GWAS) on mitochondrial proteins and neurodegenerative diseases. Bidirectional Mendelian randomization (MR), employing instrumental variables (IVs), was used to assess causal relationships. The primary method for estimating causal effects was the inverse variance-weighted (IVW) method, supplemented by additional MR approaches.

resultsBidirectional MR revealed significant associations between mitochondrial protein gene variants and neurodegenerative diseases. Specifically, associations were found with Alzheimer's disease (AD) (three proteins), Parkinson's disease (PD) (four proteins), amyotrophic lateral sclerosis (ALS) (six proteins), multiple sclerosis (two proteins), and dementia with Lewy bodies (four proteins). Conversely, analyses indicated significant associations of neurodegenerative diseases with mitochondrial protein gene variants, notably with AD, dementia with Lewy bodies, and multiple sclerosis, affecting multiple mitochondrial protein levels. Bidirectional causality was observed between dementia with Lewy bodies and C21orf33.

conclusionsUsing MR, we identified significant links between mitochondrial protein gene mutations and the risk of neurodegenerative diseases. These results highlight reciprocal relationships where certain neurodegenerative diseases influence mitochondrial protein expression levels. These findings underscore the pivotal role of mitochondrial proteins in neurodegenerative diseases, offering critical insights into disease mechanisms and potential therapeutic avenues.

Indexed as

Mendelian Randomization AnalysisMitochondrial ProteinsNeurodegenerative DiseasesGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMitochondrial Proteinsmendelian randomization analysismitochondrial proteinsneurodegenerative diseases

Identifiers

PMID39831399
PMCPMC11744296

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