Second, the sensation seeking GWAS identified variants and genes (e.g., CADM2, NF1, FOXP2, GABRA2) previously associated with indicator traits and related substance use and self‐regulatory traits. 22 , 23 , 54 , 59 Further, 31 genomic loci representing new discoveries in the documented literature were identified, 17 of which mapped to genes not previously implicated in sensation seeking or externalising behaviour GWAS, highlighting the benefit of increased power afforded by multivariate GWAS approaches for variant discovery. Gene‐based analyses suggested that positionally mapped genes for several of these novel loci have important neurobiological functions. For example, rs9944845, mapped to an intronic region of SETBP1, was associated with sensation seeking and contributed to significant associations across all gene‐based analyses. SETBP1 encodes a DNA‐binding protein involved in activating gene expression through recruitment of epigenomic protein complexes and has been linked to neurogenesis and neuronal migration. 60 A prior study also reported associations between an intergenic locus near SETBP1 and externalising behaviour that was further substantiated by gene‐based tests providing additional support for the novel result reported here. 54 Other genes showed more specific
