Investigating the genetic association of mitochondrial DNA copy number with neurodegenerative diseases
Abstract Objective This study aims to investigate the causal relationship between Mitochondrial DNA (mtDNA) copy number and several common neurodegenerative diseases (NDs). Methods We conducted a bidirectional two-sample Mendelian randomization (MR) analysis using data from genome-wide association s...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-04-01
|
| Series: | BMC Neurology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12883-025-04176-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850181175050502144 |
|---|---|
| author | Huan Xia Zi-Hao Wang Xiao-Bei Wang Mei-Rong Gao Sen Jiang Xin-Yu Du Xin-Ling Yang |
| author_facet | Huan Xia Zi-Hao Wang Xiao-Bei Wang Mei-Rong Gao Sen Jiang Xin-Yu Du Xin-Ling Yang |
| author_sort | Huan Xia |
| collection | DOAJ |
| description | Abstract Objective This study aims to investigate the causal relationship between Mitochondrial DNA (mtDNA) copy number and several common neurodegenerative diseases (NDs). Methods We conducted a bidirectional two-sample Mendelian randomization (MR) analysis using data from genome-wide association studies (GWAS) as instrumental variables (IVs). After screening for relevance and potential confounders, we estimated the association between mtDNA copy number and NDs, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS). Additionally, we validated our findings using GWAS data on mtDNA copy number from Longchamps et al., sourced from the Genetics Epidemiology Consortium and the UK Biobank (UKB) aging study cohort. Results A GWAS analysis of 395,718 UKB participants found no significant association between mtDNA copy number and the risk of NDs, including AD (OR = 0.956, P = 0.708), PD (OR = 1.223, P = 0.179), ALS (OR = 0.972, P = 0.374), and MS (OR = 0.932, P = 0.789). Similarly, reverse MR analysis revealed no significant relationship between genetic predictions of NDs and mtDNA copy number: AD (OR = 0.987, P = 0.062), PD (OR = 0.997, P = 0.514), ALS (OR = 0.974, P = 0.706), and MS (OR = 1.003, P = 0.181). Conclusion Although mitochondrial dysfunction is implicated in the pathogenesis of NDs, no clear evidence supports a causal role for mtDNA copy number. The relationship between mtDNA copy number and NDs is likely mediated by more complex molecular regulatory mechanisms. Further research is required to elucidate these intricate interactions. |
| format | Article |
| id | doaj-art-e3bc6310bece4c86aaf25fb3846834c6 |
| institution | OA Journals |
| issn | 1471-2377 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neurology |
| spelling | doaj-art-e3bc6310bece4c86aaf25fb3846834c62025-08-20T02:17:57ZengBMCBMC Neurology1471-23772025-04-012511910.1186/s12883-025-04176-7Investigating the genetic association of mitochondrial DNA copy number with neurodegenerative diseasesHuan Xia0Zi-Hao Wang1Xiao-Bei Wang2Mei-Rong Gao3Sen Jiang4Xin-Yu Du5Xin-Ling Yang6Department of Neurology, The Second Affiliated Hospital of Xinjiang Medical UniversityDepartment of Neurology, The Second Affiliated Hospital of Xinjiang Medical UniversityDepartment of Neurology, The Second Affiliated Hospital of Xinjiang Medical UniversityDepartment of Dermatology, The Second Hospital of Jilin UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurology, Jiangsu Provincial People’s HospitalXinjiang Medical UniversityAbstract Objective This study aims to investigate the causal relationship between Mitochondrial DNA (mtDNA) copy number and several common neurodegenerative diseases (NDs). Methods We conducted a bidirectional two-sample Mendelian randomization (MR) analysis using data from genome-wide association studies (GWAS) as instrumental variables (IVs). After screening for relevance and potential confounders, we estimated the association between mtDNA copy number and NDs, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS). Additionally, we validated our findings using GWAS data on mtDNA copy number from Longchamps et al., sourced from the Genetics Epidemiology Consortium and the UK Biobank (UKB) aging study cohort. Results A GWAS analysis of 395,718 UKB participants found no significant association between mtDNA copy number and the risk of NDs, including AD (OR = 0.956, P = 0.708), PD (OR = 1.223, P = 0.179), ALS (OR = 0.972, P = 0.374), and MS (OR = 0.932, P = 0.789). Similarly, reverse MR analysis revealed no significant relationship between genetic predictions of NDs and mtDNA copy number: AD (OR = 0.987, P = 0.062), PD (OR = 0.997, P = 0.514), ALS (OR = 0.974, P = 0.706), and MS (OR = 1.003, P = 0.181). Conclusion Although mitochondrial dysfunction is implicated in the pathogenesis of NDs, no clear evidence supports a causal role for mtDNA copy number. The relationship between mtDNA copy number and NDs is likely mediated by more complex molecular regulatory mechanisms. Further research is required to elucidate these intricate interactions.https://doi.org/10.1186/s12883-025-04176-7Neurodegenerative diseasesMitochondrial DNA copy numberMendelian randomization analysisGenome-wide association studies |
| spellingShingle | Huan Xia Zi-Hao Wang Xiao-Bei Wang Mei-Rong Gao Sen Jiang Xin-Yu Du Xin-Ling Yang Investigating the genetic association of mitochondrial DNA copy number with neurodegenerative diseases BMC Neurology Neurodegenerative diseases Mitochondrial DNA copy number Mendelian randomization analysis Genome-wide association studies |
| title | Investigating the genetic association of mitochondrial DNA copy number with neurodegenerative diseases |
| title_full | Investigating the genetic association of mitochondrial DNA copy number with neurodegenerative diseases |
| title_fullStr | Investigating the genetic association of mitochondrial DNA copy number with neurodegenerative diseases |
| title_full_unstemmed | Investigating the genetic association of mitochondrial DNA copy number with neurodegenerative diseases |
| title_short | Investigating the genetic association of mitochondrial DNA copy number with neurodegenerative diseases |
| title_sort | investigating the genetic association of mitochondrial dna copy number with neurodegenerative diseases |
| topic | Neurodegenerative diseases Mitochondrial DNA copy number Mendelian randomization analysis Genome-wide association studies |
| url | https://doi.org/10.1186/s12883-025-04176-7 |
| work_keys_str_mv | AT huanxia investigatingthegeneticassociationofmitochondrialdnacopynumberwithneurodegenerativediseases AT zihaowang investigatingthegeneticassociationofmitochondrialdnacopynumberwithneurodegenerativediseases AT xiaobeiwang investigatingthegeneticassociationofmitochondrialdnacopynumberwithneurodegenerativediseases AT meironggao investigatingthegeneticassociationofmitochondrialdnacopynumberwithneurodegenerativediseases AT senjiang investigatingthegeneticassociationofmitochondrialdnacopynumberwithneurodegenerativediseases AT xinyudu investigatingthegeneticassociationofmitochondrialdnacopynumberwithneurodegenerativediseases AT xinlingyang investigatingthegeneticassociationofmitochondrialdnacopynumberwithneurodegenerativediseases |