Peripheral immune cell abundance differences link blood mitochondrial DNA copy number and Parkinson's disease
- Author(s)
- Wang, L; Han, J; Fearnley, LG; Milton, M; Rafehi, H; Reid, J; Gerring, ZF; Masaldan, S; Lang, T; Speed, TP; Bahlo, M;
- Details
- Publication Year 2024-11-14,Volume 10,Issue #1,Page 219
- Journal Title
- NPJ Parkinsons Disease
- Abstract
- Mitochondrial dysfunction plays an important role in Parkinson's disease (PD), with mitochondrial DNA copy number (mtDNA-CN) emerging as a potential marker for mitochondrial health. We investigated the links between blood mtDNA-CN and PD severity and risk using the Accelerating Medicines Partnership program for Parkinson's Disease dataset, replicating our results in the UK Biobank. Our findings reveal that reduced blood mtDNA-CN levels are associated with heightened PD risk and increased severity of motor symptoms and olfactory dysfunction. We estimated blood cell composition using complete blood cell profile when available or RNA-sequencing data as a surrogate. After adjusting for blood cell composition, the associations between mtDNA-CN and PD risk and clinical symptoms became non-significant. Bidirectional Mendelian randomization analysis also found no evidence of a direct causal relationship between blood mtDNA-CN and PD susceptibility. Hence peripheral inflammatory immune responses rather than mitochondrial dysfunction underpin these previously identified associations in PD.
- Publisher
- Springer Nature
- Research Division(s)
- Bioinformatics; Ubiquitin Signalling; Population Health And Immunity
- PubMed ID
- 39543161
- Publisher's Version
- https://doi.org/10.1038/s41531-024-00831-x
- Open Access at Publisher's Site
https://doi.org/10.1038/s41531-024-00831-x- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-12-05 01:18:18
Last Modified: 2024-12-05 01:21:49