RNA alternative splicing is known to be associated with many complex diseases, especially neurological or brain disorders, including alcohol use disorder (AUD) [1–3]. AUD is a prevalent psychiatric disorder characterized by problems resulting from excessive and compulsive alcohol consumption. In the United States, AUD affects nearly 29.5 million individuals and is the third-leading preventable cause of death [4, 5]. There is a genetic component to the risk for AUD, with the estimated heritability ranging from 40% to 60% [6, 7]. Genome-wide association studies (GWAS) have identified many AUD-associated genetic variants and genes, including genes encoding the alcohol metabolizing enzymes ADH1B and ADH1C, zinc transporter SLC39A8, and neurotransmitter receptor DRD2 [8–11]. Genome-wide changes in RNA splicing were recently reported in multiple human brain regions in individuals with AUD [12, 13]. While previous research has identified alternatively spliced mRNAs induced by alcohol, whether alternative splicing impacts the susceptibility for AUD is not well studied.
