DOI: 10.1101/475111Dec 4, 2018Paper

Genetic variation within genes associated with mitochondrial function is significantly associated with later age at onset of Parkinson disease and contributes to disease risk

BioRxiv : the Preprint Server for Biology
Kimberley BillingsleySulev Koks


Mitochondrial dysfunction has been implicated in the aetiology 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. First we identified that a proportion of the missing heritability of the PD can be explained by common variation within genes implicated in mitochondrial disease (primary gene list) and mitochondrial function (secondary gene list). Next 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. Most significantly we further report 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 randomisation which showed that 14 of these mitochondrial function associate...Continue Reading

Related Concepts

Parkinson Disease
Mitochondrial Diseases
Mitochondrial Inheritance
Mitochondrial Processing
Genes, Mitochondrial

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