We found initial evidence of polygenic replication in the European ancestry sample of S4S, but not the African ancestry sample. However, the PGS were no longer significant after correcting for multiple testing. The lack of replication is most likely due to lack of power in the discovery GWAS. Other issues, including population differences (e.g. allele frequencies or LD structure), or gene-environment interactions could also influence the poor performance of PGS. Because the LD blocks in African ancestry groups are much shorter, tagging SNPs correlated with a causal SNP becomes less likely (Campbell & Tishkoff, 2008). Even larger samples likely will be necessary for gene discovery in African ancestry populations (Dick et al., 2017). Additionally, individuals of African ancestry tend to identify as African-Americans (Banda et al., 2015), and AA individuals experience more adverse environments on average compared to EA individuals (Williams & Mohammed, 2009). This is important in view of findings from twin studies that genetic influences on externalizing behaviors are reduced and shared environmental amplified in adverse environmental conditions (Tuvblad et al., 2006).
