The primary conclusion of the current study is that mRNA alternative splicing, specifically exon skipping, has a causal effect on AUD susceptibility. This conclusion is supported by the identification and replication of six exon skipping events; one was further substantiated in GWAS with diverse populations and additional AUD-related traits. Furthermore, some differentially expressed genes downstream of the identified events are known to be alcohol-responsive and associated with immunological and neurological pathways, providing additional evidence that AUD shares a genetic basis with immune and neural diseases. This knowledge advances our understanding of the contribution of RNA splicing to the genetic risk for AUD. In addition, our workflow can be a framework for splicing studies in the genetics of other complex diseases.
