that the use of the MR methodology, including the GSMR, leverages high power in causality inference from large-scale datasets. This method enables identification of causal splicing events, which provides new information on the role of RNA splicing in AUD risk. The new information regarding the downstream genes and pathways implicated by the splicing events provides evidence of causality for findings from previous GWAS and differential gene expression studies, as well as sheds new insights in the molecular mechanisms contributing to AUD. For example, targeting an alternatively spliced exon identified herein an experimental model system relevant to AUD could provide further verification. Together, our results advance the field of AUD research and our method provides a framework for studying RNA splicing in complex genetic diseases.
