We found that the degree to which exon skipping was genetically determined varied widely. For example, in NMRK1 (Nicotinamide Riboside Kinase 1), a key enzyme in the synthesis of NAD+, the PSI of exon ENSE00000707111 was highly cis-regulated (R2 = 0.847, Fig. 1C). In contrast, in SYNGAP1 (Synaptic Ras GTPase Activating Protein 1), a gene associated with AUD and involved in regulating synaptic plasticity and neuronal homeostasis [11], exon ENSE00001930700 showed a low degree of cis-regulation (R2 = 13.5%, Fig. 1D). Our results are consistent with the notion that complex regulatory mechanisms influence splicing outcomes and that genetic variants are only one of several contributing factors.
