Table 1.
SNP | Gene | MAF | Odds Ratio | Known function | Related AD Risk Genes | Potential Effects on APP and Tau | Pathways | Gene Expression |
---|---|---|---|---|---|---|---|---|
APP | Neurite outgrowth, adhesion and axonogenesis | Cleavage yields Aβ | APP processing | |||||
PSEN1 | Component of catalytic subunit of gamma-secretase complex. Proteolytic cleavage of integral membrane proteins | Cleaves APP | APP processing | |||||
PSEN2 | Component of catalytic subunit of gamma-secretase complex. Proteolytic cleavage of integral membrane proteins | Cleaves APP | APP processing | |||||
APOE | Mediates binding, internalization and catabolism of lipoproteins | SORL1 | Aβ clearance | Lipid Metabolism | ||||
ADAM10 | Proteolytic cleavage of integral membrane proteins | Cleaves APP | APP processing | |||||
rs6656401 | CR1a | 0.197 | 1.18 | Mediates cellular binding of immune complexes that activate complement | Aβ clearance | Immune Response | Increased | |
rs6733839 | BIN1b | 0.409 | 1.22 | Regulation of endocytosis of synaptic vesicles | SLC24A4 & RIN3 | Mediates tau toxicity | Synapse function | Increased |
rs10948363 | CD2AP | 0.266 | 1.1 | Scaffold molecule regulating actin cytoskeleton | INPP5D & CASS4 | Mediates tau toxicity | Synapse function & Endocytosis | No change |
rs11771145 | EPHA1c | 0.338 | 0.9 | Brain and neural development. Angiogenesis, cell proliferation, and apoptosis | N/A | Immune Response & Neural Development | No change | |
rs9331896 | CLU | 0.379 | 0.86 | Chaperone. Regulation of cell proliferation. | PTK2B | Aβ clearance | Immune Response & Lipid Metabolism | Increased |
rs983392 | MS4A6Ad | 0.403 | 0.9 | Signal transduction | N/A | Immune Response | No change | |
rs10792832 | PICALMe | 0.358 | 0.87 | AP2-dependent clathrin mediated endocytosis | APP trafficking & Aβ clearance | Synapse function & Endocytosis | No change | |
rs4147929 | ABCA7f | 0.19 | 1.15 | Lipid homeostasis. Phagocytosis of apoptotic cells by macrophages | Aβ clearance | Immune Response & Lipid Metabolism | Increased | |
rs3865444 | CD33 | 0.307 | 0.94 | Mediates sialic acid-dependent binding to cells | Aβ clearance | Immune Response | Increased | |
rs9271192 | HLA-DRB5 HLA- DRB1g | 0.276 | 1.11 | Immunocompetence and histocompatibility | N/A | Immune Response | N/A | |
rs28834970 | PTK2B | 0.366 | 1.1 | Induction of long term potentiation in hippocampus | CLU | N/A | Synapse function & Neural Development | N/A |
rs11218343 | SORL1 | 0.039 | 0.77 | APOE receptor. Binds LDL and RAP and mediates endocytosis of the lipids to which it binds | APOE | APP trafficking | Lipid Metabolism, Synapse Function & Endocytosis | Decreased |
rs10498633 | SLC24A4 & RIN3 | 0.217 | 0.91 | Brain and neural development (SLC24A4); Stimulates & stabilizes GTP-Rab5 in protein transport from plasma membrane to early endosome (RIN3) | BIN1 | N/A | Neural Development, Synapse Function & Endocytosis | N/A |
rs8093731 | DSG2h | 0.017 | 0.73 | Mediates cell-cell junctions between epithelial and other cell type. | N/A | N/A | N/A | |
rs35349669 | INPP5D | 0.488 | 1.08 | Negative regulator of myeloid cell proliferation and survival | CD2AP | N/A | Immune Response | N/A |
rs190982 | MEF2C | 0.408 | 0.93 | Controls synapse formation during activity-dependent refinement of synaptic connectivity and facilitates hippocampal-dependent learning and memory | N/A | Neural Development, Synapse Function & Immune Response | N/A | |
rs2718058 | NME8i | 0.373 | 0.93 | Ciliary functions | N/A | N/A | N/A | |
rs1476679 | ZCWPW1 & NYAP1j | 0.287 | 0.91 | Epigenetic regulation (ZCWPW1); Brain and neural development (NYAP1) | N/A | Neural Development | N/A | |
rs10838725 | CELF1 & MADDk | 0.316 | 1.08 | Regulates pre-mRNA splicing (CELF1); Long-term neuronal viability (MADD) | Mediates tau toxicity | Neural Development | N/A | |
rs17125944 | FERMT2 | 0.092 | 1.14 | Actin assembly and cell shape and mediator of angiogenesis | Mediates tau toxicity | Cytoskeleton & Axonal transport | N/A | |
rs7274581 | CASS4l | 0.083 | 0.88 | Docking protein in tyrosine-kinase signaling involved in cell adhesion and spreading | CD2AP | N/A | Cytoskeleton & Axonal transport | N/A |
rs75932628 | TREM2 | 0.049 | 2.55 | Immune response, triggers production of inflammatory cytokines | Aβ clearance | Immune Response | N/A | |
rs145999145 | PLD3 | 0.06 | 2.75 | Unknown | APP trafficking and cleavage | Unknown | Increased |
Additional genes located within GWAS loci:
A, CR2, CR1L
B, CYP27C1
C, LOC285965, TAS2R60
D, MS4A3, MS4A2, MS4A6A, MS4A4A, MS4A6E
E, EED
F, CNN2, POLR3E, GPX4
G, HLA-DRB6, HLA-DQA1, HLA-DQB1
H, GSG2
I, GPR141
J, PMS2P1, PILRB, PILRA, C7ORF61, C7ORF47, MEPCE
K, SLC39A13, PSMC3, NDUFS3, KBTBD4, PTPMT1, MTCH2, AGBL2, FNBP4, NUP160
L, C20ORF43, CSTF1