APOE and major depressive disorder: Candidate gene and genome-wide association studies (GWAS) of AD have identified a number of variants associated with risk of developing late-onset AD, which accounts for over 95% of AD cases.20, 21 Common single-nucleotide polymorphisms (SNPs) explain 33% of the total phenotypic variance, with the strongest genetic risk factor being the APOE ɛ4 allele.22 MDD is a complex and phenotypically heterogeneous disorder, influenced by both genetic and environmental factors.