Human brain single nucleus cell type enrichments in neurodegenerative diseases.
Chelsea X AlvaradoCory A WellerNicholas JohnsonHampton L LeonardAndrew B SingletonXylena ReedCornelis BlauewendraatMike NallsPublished in: medRxiv : the preprint server for health sciences (2023)
Single cell RNA sequencing has opened a window into clarifying the complex underpinnings of disease, particularly in quantifying the relevance of tissue- and cell-type-specific gene expression. To identify the cell types and genes important to therapeutic target development across the neurodegenerative disease spectrum, we leveraged genome-wide association studies, recent single cell sequencing data, and bulk expression studies in a diverse series of brain region tissues. We were able to identify significant immune-related cell types in the brain across three major neurodegenerative diseases: Alzheimer's Disease, Amyotrophic Lateral Sclerosis, and Parkinson's Diseases. Subsequently, we identified the major role of 30 fine-mapped loci implicating seven genes in multiple neurodegenerative diseases and their pathogenesis.
Keyphrases
- single cell
- rna seq
- gene expression
- high throughput
- amyotrophic lateral sclerosis
- genome wide association
- genome wide
- resting state
- white matter
- dna methylation
- case control
- stem cells
- functional connectivity
- bone marrow
- multiple sclerosis
- deep learning
- machine learning
- electronic health record
- genome wide identification
- bioinformatics analysis
- mesenchymal stem cells
- long non coding rna
- artificial intelligence
- brain injury
- drug induced
- genome wide analysis