RNA sequence analysis of somatic mutations in aging and Parkinson's Disease

Abstract

Parkinsons Disease (PD) is an age-related neurodegenerative disorder that has been associated with increased DNA damage. To test if PD is associated with increased somatic mutations, we analyzed RNA-seq data in whole blood from 5 visits of the Parkinsons Progression Markers Initiative for clonally amplified somatic variants. Comprehensive analysis of RNA-sequencing data revealed a total of 5,927 somatic variants (2.4 variants per sample on average). Mutation frequencies were significantly elevated in PD subjects as compared to age-matched controls at the time of the last visit. This was confirmed by RNA analysis of substantia nigra. By contrast, the fraction of carriers with clonal hematopoiesis, was significantly reduced in old PD patients as compared to old healthy controls. These results indicate that while the overall mutation rate is higher in PD, specific clonally amplified mutations are protective against PD, as has been found for Alzheimers Disease.