Multivariate GWAS were conducted to estimate SNP associations with sensation seeking and alcohol consumption latent factors separately (i.e., single factor models) using GenomicSEM (see Supporting Information Methods). Individual effects for SNPs available across all indicator GWAS and present in the 1000 Genomes Project Phase 3 v5 reference panel 41 were estimated for each trait. Effective sample sizes (N^) were estimated using the approach described by Mallard et al. 42 SNP‐based heritability estimates (hg2) for latent genomic factors are more accurately referred to as genetic variances, and thus are subsequently denoted by ζ g . Follow‐up multivariate GWAS that included unique pathways from SNPs to each indicator were conducted to calculate Q SNP heterogeneity tests. 35 SNPs with genome‐wide significant (GWS) Q SNP statistics (P < 5 × 10−8) reflect associations not fully mediated by the latent genomic factor (i.e., common pathway model). These were removed from downstream analyses to reduce heterogeneity (Figure S2).
