APOE and major depressive disorder: A number of studies have suggested that the known AD risk genes APOE and CR1 are also associated with MDD,26, 27, 28, 29 although these were candidate gene studies with small sample sizes, and the findings were inconsistent.30, 31 However, both disorders are highly polygenic,18, 19 and any genetic overlap could extend well beyond a few individual genes, although there is little evidence of this to date.