Genetic analysis of amyotrophic lateral sclerosis identifies contributing pathways and cell types.

ABSTRACT: Despite the considerable progress in unraveling the genetic causes of amyotrophic lateral sclerosis (ALS), we do not fully understand the molecular mechanisms underlying the disease. We analyzed genome-wide data involving 78,500 individuals using a polygenic risk score approach to identify the biological pathways and cell types involved in ALS. This data-driven approach identified multiple aspects of the biology underlying the disease that resolved into broader themes, namely, neuron projection morphogenesis, membrane trafficking, and signal transduction mediated by ribonucleotides. We also found that genomic risk in ALS maps consistently to GABAergic interneurons and oligodendrocytes, as confirmed in human single-nucleus RNA-seq data. Using two-sample Mendelian randomization, we nominated

SUBMITTER: Saez-Atienzar S 

PROVIDER: S-EPMC7810371 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature