Multi-omics integration analysis identifies novel genes for alcoholism with potential link to neurodegenerative diseases

Alcohol use disorders (AUD) are complex, moderately heritable, psychiatric disorders associated with heightened morbidity and mortality. Genome-wide association studies of AUD and drinks per week (DPW) have identified multiple risk loci however few studies have examined the intersection between the loci and genes associated with AUD and DPW, especially with respect to their functional and regulatory significance. In this study we use a muti-omics systems approach to identify causal variants and genes associated with AUD and DPW. We used Mendelian randomization to integrate AUD and drinks per week GWAS summary statistics with gene expression and methylation quantitative trait loci in the largest brain and myeloid datasets as well as AUD-related single cell epigenetic data to nominate candidate causal variants and genes associated with DPW and AUD.