Journal article
Mitochondria function associated genes contribute to Parkinson’s Disease risk and later age at onset
npj Parkinson's Disease, Vol.5(1)
2019
Abstract
Mitochondrial dysfunction has been implicated in the etiology of monogenic Parkinson’s disease (PD). Yet the role that mitochondrial processes play in the most common form of the disease; sporadic PD, is yet to be fully established. Here, we comprehensively assessed the role of mitochondrial function-associated genes in sporadic PD by leveraging improvements in the scale and analysis of PD GWAS data with recent advances in our understanding of the genetics of mitochondrial disease. We calculated a mitochondrial-specific polygenic risk score (PRS) and showed that cumulative small effect variants within both our primary and secondary gene lists are significantly associated with increased PD risk. We further reported that the PRS of the secondary mitochondrial gene list was significantly associated with later age at onset. Finally, to identify possible functional genomic associations we implemented Mendelian randomization, which showed that 14 of these mitochondrial function-associated genes showed functional consequence associated with PD risk. Further analysis suggested that the 14 identified genes are not only involved in mitophagy, but implicate new mitochondrial processes. Our data suggests that therapeutics targeting mitochondrial bioenergetics and proteostasis pathways distinct from mitophagy could be beneficial to treating the early stage of PD
Details
- Title
- Mitochondria function associated genes contribute to Parkinson’s Disease risk and later age at onset
- Authors/Creators
- K.J. Billingsley (Author/Creator)I.A. Barbosa (Author/Creator)S. Bandrés-Ciga (Author/Creator)J.P. Quinn (Author/Creator)V.J. Bubb (Author/Creator)C. Deshpande (Author/Creator)J.A. Botia (Author/Creator)R.H. Reynolds (Author/Creator)D. Zhang (Author/Creator)M.A. Simpson (Author/Creator)C. Blauwendraat (Author/Creator)Z. Gan-Or (Author/Creator)J.R. Gibbs (Author/Creator)M.A. Nalls (Author/Creator)A. Singleton (Author/Creator)M. Ryten (Author/Creator)S. Kõks (Author/Creator)
- Publication Details
- npj Parkinson's Disease, Vol.5(1)
- Publisher
- Nature Publishing Group
- Identifiers
- 991005543695607891
- Copyright
- © 2019 Springer Nature Publishing AG
- Murdoch Affiliation
- Centre for Comparative Genomics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.52 Neurodegenerative Diseases
- 1.52.67 Parkinson's Disease
- Web Of Science research areas
- Neurosciences
- ESI research areas
- Neuroscience & Behavior