Parkinson Disease study with ATAC-seq, RNA-Seq data on dbGaP (34 participants)

phs002819 — Single-Nuclei Paired Multiomic Analysis of Young, Aged, and Parkinson's    Disease Human Midbrain Reveals Age-Associated Glial Changes and Their    Contribution to Parkinson's Disease

<p>Age is the primary risk factor for Parkinson's disease (PD), but how aging to change the expression and regulatory landscape of the brain remains unclear. Here, we present a single-nuclei multiomic study profiling shared gene expression and chromatin accessibility of young, aged and PD post-mortem midbrain samples. Combined multiomic analysis of midbrain nuclei along a pseudo-pathogenesis trajectory reveals that all glial cell types are affected by age, but microglia and oligodendrocytes are further altered in PD. We present evidence for a novel disease-associated oligodendrocyte subtype and identify genes lost over the aging and disease process, including <a href="https://www.ncbi.nlm.nih.gov/gene/57571">CARNS1</a>, that may predispose healthy cells to develop a disease-associated phenotype. Peak-gene association analysis from paired data identifies 89 PD-associated SNP loci, including five in <a href="https://www.ncbi.nlm.nih.gov/gene/4137">MAPT</a>, that only correlate with gene expression in disease-associated oligodendrocytes. Our study suggests a previously undescribed role for oligodendrocytes in aging and PD pathogenesis.</p>

Single-Nuclei Paired Multiomic Analysis of Young, Aged, and Parkinson's    Disease Human Midbrain Reveals Age-Associated Glial Changes and Their    Contribution to Parkinson's Disease