Background: 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.
Methods: 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.
Results: 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 disease. Subsequently, putative roles of 30 fine-mapped loci implicating seven genes in multiple neurodegenerative diseases and their pathogenesis were identified.
Conclusions: We have helped refine the genetic regions and cell types effected across multiple neurodegenerative diseases, helping focus future translational research efforts.
Keywords: MAGMA; Neurodegenerative diseases; colocalization; single nucleus cell expression.