Following the GWAS, we performed post-hoc analyses to further assess the impact of the APOE and BCHE loci on Aβ burden. While both the APOE ε4 allele and the minor allele (G) of rs509208 conferred increases in cortical Aβ levels (Figure 4A and 4B), there was no evidence of epistasis modeled as an interaction between these factors (p = 0.871). Instead, these factors appeared to exert independent and additive effects on Aβ burden (Figure 4C), with comparable effect size associated with presence of at least one copy of the minor allele at rs509208 whether APOE ε4 allele status was included as a covariate (Cohen’s d = 0.50) or not (Cohen’s d = 0.52). Exploratory analyses did not reveal significant interactions (p > 0.05) of the APOE or BCHE risk loci with age, diagnosis, education, or gender.
