We estimated partitioned h2 SNP using genomic features or functional categories28 for both AUDIT-C and AUD in the largest dataset, EAs, and then tested for enrichment of the partitioned h2 SNP in different annotations. First, we used a baseline model consisting of 53 functional categories, including UCSC gene models [exons, introns, promotors, untranslated regions (UTRs)], ENCODE functional annotations51, Roadmap epigenomic annotations52, and FANTOM5 enhancers53. We then analyzed cell type-specific annotations and identified enrichments of h2 SNP in 10 cell types, including adrenal and pancreas, CNS, cardiovascular, connective tissue and bone, gastrointestinal, immune and hematopoietic, kidney, liver, skeletal muscle and other. Gene expression and chromatin data were also analyzed to identify disease-relevant tissues, cell types, and tissue-specific epigenetic annotations. We used LDSC to test for enriched heritability in regions surrounding genes with the highest tissue-specific expression or with epigenetic marks29. Sources of data that were analyzed included 53 human tissue or cell type RNA-seq data from the Genotype-Tissue Expression Project (GTEx)54; 152 human, mouse, or rat tissue or cell type array data from the Franke lab;55 3 sets of mouse brain
