To test whether differentially spliced genes associated with AUD in the brain pointed to genetic mechanisms of alcohol misuse we performed a partitioned heritability analysis. We used LD score regression31 and created an annotated gene set of differentially spliced genes (BH-FDR < 0.05). To be consistent with our sQTL analyses, this included SNPs within 1 Mb of the start and stop site of a differentially spliced gene, which is similar to defaults on other splicing partitioned heritability mapping tools (e.g., Li et al.32). To determine the specificity of our findings, we tested the partitioned heritability of this gene-set with a negative control trait (Joint disorders found via: http://www.nealelab.is/uk-biobank) that used individuals of European ancestry and had similar sample size (n = ~ 361,194) and trait heritability (h2SNP = 0.0695) as AUD.
