Peripheral immune cell abundance differences link blood mitochondrial DNA copy number and Parkinson’s disease
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.
Citation
@article{wang2022,
author = {Wang, Longfei and Han, Jiru and G. Fearnley, Liam and
Milton, Michael and Rafehi, Haloom and Reid, Joshua and F. Gerring,
Zachary and Masaldan, Shashank and Lang, Tali and P. Speed, Terence
and Bahlo, Melanie},
title = {Peripheral Immune Cell Abundance Differences Link Blood
Mitochondrial {DNA} Copy Number and {Parkinson’s} Disease},
journal = {npj Parkinson’s Disease},
volume = {10},
date = {2022-11-14},
url = {https://doi.org/10.1038/s41531-024-00831-x},
doi = {10.1038/s41531-024-00831-x},
langid = {en},
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.}
}