NOS3 and Alzheimer disease: In the reconstructed AD variant-variant PPI network, we observed that the ESR1 gene interacts with several susceptibility genes, including UBE2I, TP53, SETD7, RPS6KB2, PPARG, PARP1, NTRK1, NOS3, MMP9, MAPK1, IGF1, ESR2, EGFR, DROSHA, CTSD, CD44, BRCA2, BCL2, and AKT1 (Figure 11).