Perturb-seq analysis using genes associated with alcohol consumption and alcohol use disorder

To approach this, we evaluated the impact of variants in 3’ untranslated regions (3’-UTRs) of genes in loci associated with substance use and neurological disorders using a massively parallel reporter assay (MPRA) in neuroblastoma and microglia cells.

We identified genes whose 3’-UTR activities are associated with AUD and alcohol consumption by combining variant effects from MPRA with GWAS results. We examined their effects by evaluating gene expression after CRISPR inhibition of neuronal cells.