Fig. 8

Association interpretation in the visualized phenotype description network for AD. a Observation of the gene-phenotype links. There are 19 significant PheSeq genes linked with the phenotype term “apoptosis process” in AD, and sequence analysis provides 7 significant links. b Gene-gene interaction through genes with shared phenotype descriptions. APOE and PSEN1 inhibit the autophagy of mitochondria directly, as reported in PMID:33440662 [95] and PMID:31720366 [96]. Meanwhile, PSNE1 inhibits this biological process by affecting PINK1 and PARK2. c Multiple GO terms lead to complex gene pathological pathways. PSEN1 and GSK3B are exclusively found in PheSeq, while the other four, i.e., APOE, MAPT, APP, and PICALM are both found by PheSeq and IGAP GWAS. All of them interact with each other and lead to two biological processes, long-term synaptic potentiation, and synaptic transmission. d Links between genes and GO or HPO interpret a multi-level pathology mechanism. By tracing two HPO terms, i.e., neuronal loss in the central nervous system and neurodegeneration, to GO terms and their linked genes, multi-level links are formulated. Three genes are included in these links, in which GSK3B is exclusively found by PheSeq, while APP and MAPT are separately found by PheSeq and IGAP GWAS. These links unveil a cascade mechanism that starts from gene involvement in multiple biological processes and ends in two phenotypic processes