We found preliminary evidence that alternative mRNA splicing could play a more general role in a common genetic liability of substance use disorders and psychopathology. Our study revealed moderate splicing associations across disordered and problematic drug use as well as tobacco consumption, via splicing TWASs. Furthermore, the sQTLs underlying AUD-related differential splicing in the brain were correlated with DNA variants previously implicated in tobacco consumption, mental illness, and cognitive functioning. Additionally, differentially spliced genes correlated with AUD in our analyses were also linked with brain splicing associations with autism spectrum disorder and schizophrenia2, which included glutamate receptor (GRIA2) and calcium signaling genes (CACNA1G, CAMK2D, and CAMKMT) as well as intracellular processes (AKAP13, ARPP21, PRKACB, and PTPRS) and synaptic plasticity genes (ARHGEF10L, ARHGEF4, CLASP2, GAPVD1, NTNG2, SUN1, and TPM3).
