In order to validate the results from the current GWAS, we employed a series of follow up analyses. First, we meta-analyzed GWAS results across COGA and S4S (referred to as cross-sample meta analysis) in METAL using an sample-size weighted approach (Willer et al., 2010) to examine whether the inclusion of additional samples improved estimates for top SNPs in the within COGA meta-analysis. Second, we examined whether genome-wide significant or suggestive SNPs identified in the within COGA meta analysis were associated with externalizing in S4S. Because we were underpowered to detect individual SNP effects, we also employed a “holistic replication” strategy used by others in gene-identification (Karlsson Linnér et al., 2019; Okbay et al., 2016) that assessed the number of lead SNPs with concordant signs, the number of lead SNPs with p ≤ 0.05, and the proportion of lead SNPs with p ≤ 0.05 given all lead SNPs in the validation cohort.
