Mitochondria function associated genes contribute to Parkinson’s Disease risk and later age at onset
Metadatos
Afficher la notice complèteAuteur
Billingsley, Kimberley J.; International Parkinson’s Disease Genomics Consortium; Barrero Hernández, Francisco Javier; Vives Montero, Francisco; Durán Ogalla, RaquelEditorial
Nature Research
Date
2019-05-22Referencia bibliográfica
Billingsley, K.J., Barbosa, I.A., Bandrés-Ciga, S. et al. Mitochondria function associated genes contribute to Parkinson’s Disease risk and later age at onset. npj Parkinsons Dis. 5, 8 (2019). [https://doi.org/10.1038/s41531-019-0080-x]
Patrocinador
This work was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services; project ZO1 AG000949Résumé
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 functionassociated
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.