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...

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Published in:NPJ Parkinson's Disease 2024-11, Vol.10 (1), p.219-10, Article 219
Main Authors: Wang, Longfei, Han, Jiru, Fearnley, Liam G., Milton, Michael, Rafehi, Haloom, Reid, Joshua, Gerring, Zachary F., Masaldan, Shashank, Lang, Tali, Speed, Terence P., Bahlo, Melanie
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631/114/2163
692/53/2421
Biobanks
Biomarkers
Biomedical and Life Sciences
Biomedicine
Blood
Blood platelets
Disease
Estimates
Genetic testing
Genomes
Medical research
Mitochondrial DNA
Neurology
Neurosciences
Parkinson's disease
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container_title NPJ Parkinson's Disease
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creator Wang, Longfei
Han, Jiru
Fearnley, Liam G.
Milton, Michael
Rafehi, Haloom
Reid, Joshua
Gerring, Zachary F.
Masaldan, Shashank
Lang, Tali
Speed, Terence P.
Bahlo, Melanie
description 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.
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subjects 631/114/2163
692/53/2421
Biobanks
Biomarkers
Biomedical and Life Sciences
Biomedicine
Blood
Blood platelets
Disease
Estimates
Genetic testing
Genomes
Medical research
Mitochondrial DNA
Neurology
Neurosciences
Parkinson's disease
title Peripheral immune cell abundance differences link blood mitochondrial DNA copy number and Parkinson’s disease
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