RT Journal Article
T1 Mitochondria function associated genes contribute to Parkinson's Disease risk and later age at onset.
A1 Billingsley, Kimberley J
A1 Barbosa, Ines A
A1 Bandrés-Ciga, Sara
A1 Quinn, John P
A1 Bubb, Vivien J
A1 Deshpande, Charu
A1 Botia, Juan A
A1 Reynolds, Regina H
A1 Zhang, David
A1 Simpson, Michael A
A1 Blauwendraat, Cornelis
A1 Gan-Or, Ziv
A1 Gibbs, J Raphael
A1 Nalls, Mike A
A1 Singleton, Andrew
A1 International Parkinson’s Disease Genomics Consortium (IPDGC), 
A1 Ryten, Mina
A1 Koks, Sulev
K1 Medical genetics
K1 Risk factors
AB 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.
SN 2373-8057
YR 2019
FD 2019-05-22
LK https://hdl.handle.net/10668/26040
UL https://hdl.handle.net/10668/26040
LA en
DS RISalud
RD Apr 12, 2025