Gene, cell type, and drug prioritization analysis suggest genetic basis for the utility of diuretics in treating Alzheimer disease.

We introduce a user-friendly tool for risk gene, cell type, and drug prioritization for complex traits: GCDPipe. It uses gene-level GWAS-derived data and gene expression data to train a model for the identification of disease risk genes and relevant cell types. Gene prioritization information is then coupled with known drug target data to search for applicable drug agents based on their estimated functional effects on the identified risk genes. We illustrate the utility of our approach in different settings: identification of the cell types, implicated in disease pathogenesis, was tested in inflammatory bowel disease (IBD) and Alzheimer disease (AD); gene target and drug prioritization was tested in IBD and schizophrenia. The analysis of phenotypes with known disease-affected cell types and/or existing drug candidates shows that GCDPipe is an effective tool to unify genetic risk factors with cellular context and known drug targets. Next, analysis of the AD data with GCDPipe suggested that gene targets of diuretics, as an Anatomical Therapeutic Chemical drug subgroup, are significantly enriched among the genes prioritized by GCDPipe, indicating their possible effect on the course of the disease.

GWAS of depression in 4,520 individuals from the Russian population highlights the role of MAGI2 (S-SCAM) in the gut-brain axis.

We present the results of the depression Genome-wide association studies study performed on a cohort of Russian-descent individuals, which identified a novel association at chromosome 7q21 locus. Gene prioritization analysis based on already known depression risk genes indicated MAGI2 (S-SCAM) as the most probable gene from the locus and potential susceptibility gene for the disease. Brain and gut expression patterns were the main features highlighting functional relatedness of MAGI2 to the previously known depression risk genes. Local genetic covariance analysis, analysis of gene expression, provided initial suggestive evidence of hospital anxiety and depression scale and diagnostic and statistical manual of mental disorders scales having a different relationship with gut-brain axis disturbance. It should be noted, that while several independent methods successfully in silico validate the role of MAGI2, we were unable to replicate genetic association for the leading variant in the MAGI2 locus, therefore the role of rs521851 in depression should be interpreted with caution.