| Title: | Peripheral immune cell abundance differences link blood mitochondrial DNA copy number and Parkinson's disease |
| Journal: | npj Parkinson's Disease |
| Published: | 14 Nov 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39543161/ |
| DOI: | https://doi.org/10.1038/s41531-024-00831-x |
Publication 14187
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
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.</p>
11 Authors
- Longfei Wang
- Jiru Han
- Liam G. Fearnley
- Michael Milton
- Haloom Rafehi
- Joshua Reid
- Zachary F. Gerring
- Shashank Masaldan
- Tali Lang
- Terence P. Speed
- Melanie Bahlo
1 Application
| Application ID | Title |
|---|---|
| 36610 | Exploring the genetic basis of healthy development and ageing: gene discovery and methods development. |
Enabling scientific discoveries that improve human health