Table 1 Proteins showing a significant association with Alzheimer’s disease risk for their genetically predicted concentrations in plasma
Protein | Protein full name | SOMAMER ID | Encoding gene ID | Modeling methoda | Num of predicting SNPs in model | Num of predicting SNPs-Cisb | Num of predicting SNPs-Trans | Model internal cross validation R2 | Model external validation R2 | Z scorec | P-value | Distance of gene to closest risk SNP (kb)d |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
TBCA | Tubulin-specific chaperone A | TBCA.12501.10.3 | TBCA | blup | 470 | 0 | 470 | 0.54 | 0.51 | − 50.90 | < 1.09 × 10−298 | 9,236.20 |
S100A13 | Protein S100-A13 | S100A13.7223.60.3 | S100A13 | blup | 528 | 0 | 528 | 0.56 | 0.54 | − 39.10 | < 1.09 × 10−298 | 7,564.12 |
DCK | Deoxycytidine kinase | DCK.9836.20.3 | DCK | lasso | 5 | 0 | 5 | 0.04 | 0.02 | 19.80 | 7.23 × 10−87 | 31,660.52 |
PSME1 | Proteasome activator complex subunit 1 | PSME1.5918.5.3 | PSME1 | lasso | 13 | 0 | 13 | 0.19 | 0.11 | − 19.00 | 8.12 × 10−81 | 28,693.45 |
SYVC | Valine–tRNA ligase | VARS.13083.18.3 | VARS | enet | 69 | 0 | 69 | 0.38 | 0.27 | 16.90 | 2.71 × 10−64 | 833.24 |
PSG5 | Pregnancy-specific beta-1-glycoprotein 5 | PSG5.9314.9.3 | PSG5 | enet | 50 | 16 | 34 | 0.07 | 0.05 | 16.90 | 8.68 × 10−64 | 1,740.05 |
UBP21 | Ubiquitin carboxyl-terminal hydrolase 21 | USP21.12681.63.3 | USP21 | enet | 39 | 0 | 39 | 0.14 | 0.08 | 15.90 | 3.69 × 10−57 | 26.10 |
SURF1 | Surfeit locus protein 1 | SURF1.8009.121.3 | SURF1 | enet | 68 | 0 | 68 | 0.06 | 0.05 | 15.80 | 1.62 × 10−56 | 28,552.64 |
RPAC1 | DNA-directed RNA polymerases I and III subunit RPAC1 | POLR1C.12939.1.3 | POLR1C | enet | 44 | 0 | 44 | 0.03 | 0.01 | 15.30 | 6.67 × 10−53 | 2,542.63 |
P5I11 | Tumor protein p53-inducible protein 11 | TP53I11.13022.20.3 | TP53I11 | enet | 19 | 0 | 19 | 0.06 | 0.05 | 15.20 | 2.25 × 10−52 | 2,426.44 |
NRBP | Nuclear receptor-binding protein | NRBP1.12616.45.3 | NRBP1 | enet | 40 | 11 | 29 | 0.07 | 0.02 | 14.90 | 3.56 × 10−50 | 9,881.28 |
MO2R2 | Cell surface glycoprotein CD200 receptor 2 | CD200R1L.8980.19.3 | CD200R1L | top1 | 1 | 0 | 1 | 0.09 | 0.03 | − 13.30 | 4.44 × 10−40 | 42,252.95 |
APBB2 | Amyloid beta A4 precursor protein-binding family B member 2 | APBB2.12753.6.3 | APBB2 | top1 | 1 | 0 | 1 | 0.05 | 0.03 | − 13.20 | 8.33 × 10−40 | 613.20 |
MUCDL | Cadherin-related family member 5 | CDHR5.9962.1.3 | CDHR5 | top1 | 1 | 0 | 1 | 0.03 | 0.02 | 13.10 | 2.66 × 10−39 | 46,763.76 |
TM59L | Transmembrane protein 59-like | TMEM59L.9959.60.3 | TMEM59L | enet | 47 | 0 | 47 | 0.05 | 0.01 | 12.40 | 2.48 × 10−35 | 16,869.43 |
EMAP-2 | Endothelial monocyte-activating polypeptide 2 | AIMP1.2714.78.2 | AIMP1 | lasso | 4 | 0 | 4 | 0.06 | 0.03 | 11.50 | 1.51 × 10−30 | 67,037.86 |
MED4 | Mediator of RNA polymerase II transcription subunit 4 | MED4.14021.81.3 | MED4 | top1 | 1 | 0 | 1 | 0.09 | 0.05 | 11.10 | 7.48 × 10−29 | NAd |
QORL1 | Quinone oxidoreductase-like protein 1 | CRYZL1.9207.60.3 | CRYZL1 | enet | 18 | 0 | 18 | 0.16 | 0.13 | 11.10 | 7.76 × 10−29 | 7,440.72 |
GST M1-1 | Glutathione S-transferase Mu 1 | GSTM1.7239.9.3 | GSTM1 | enet | 20 | 6 | 14 | 0.03 | 0.05 | 10 | 1.03 × 10−23 | 342.01 |
XRCC4 | DNA repair protein XRCC4 | XRCC4.9886.28.3 | XRCC4 | lasso | 4 | 0 | 4 | 0.05 | 0.03 | 9.43 | 3.98 × 10−21 | 3,849.83 |
Cofilin-1 | Cofilin-1 | CFL1.4203.50.2 | CFL1 | lasso | 6 | 0 | 6 | 0.11 | 0.08 | 9.04 | 1.59 × 10−19 | 5,600.20 |
MAPK5 | MAP kinase-activated protein kinase 5 | MAPKAPK5.8382.47.3 | MAPKAPK5 | lasso | 21 | 0 | 21 | 0.48 | 0.49 | 8.79 | 1.48 × 10−18 | 1,439.76 |
SULT 1E | Estrogen sulfotransferase | SULT1E1.9878.3.3 | SULT1E1 | lasso | 10 | 0 | 10 | 0.11 | 0.05 | − 8.08 | 6.54 × 10−16 | 30,508.08 |
Testican-1 | Testican-1 | SPOCK1.5490.53.3 | SPOCK1 | enet | 24 | 0 | 24 | 0.05 | 0.01 | 7.38 | 1.63 × 10−13 | 14,121.40 |
LRTM2 | Leucine-rich repeat and transmembrane domain-containing protein 2 | LRTM2.8906.60.3 | LRTM2 | enet | 49 | 0 | 49 | 0.04 | 0.01 | 6.70 | 2.03 × 10−11 | 111,790.06 |
APRV1 | Retroviral-like aspartic protease 1 | ASPRV1.13023.8.3 | ASPRV1 | enet | 42 | 0 | 42 | 0.14 | 0.12 | 6.59 | 4.26 × 10−11 | 32,627.91 |
PRPC | Salivary acidic proline-rich phosphoprotein 1/2 | PRH1.10502.15.3 | PRH1 | enet | 38 | 21 | 17 | 0.05 | 0.04 | 6.53 | 6.52 × 10−11 | 102,686.22 |
Furin | Furin | FURIN.6276.16.3 | FURIN | enet | 43 | 0 | 43 | 0.07 | 0.05 | 6.51 | 7.76 × 10−11 | 12,182.62 |
SL9B2 | Mitochondrial sodium/hydrogen exchanger 9B2 | SLC9B2.9088.20.3 | SLC9B2 | lasso | 4 | 0 | 4 | 0.02 | 0.02 | 6.48 | 9.02 × 10−11 | 63,740.34 |
Gc-Globulin, Mixed Type | Vitamin D-binding protein | GC.6581.50.3 | GC | enet | 30 | 0 | 30 | 0.17 | 0.16 | 6.40 | 1.53 × 10−10 | 32,408.56 |
PRB4 | Basic salivary proline-rich protein 4 | PRB4.12590.67.3 | PRB4 | top1 | 1 | 0 | 1 | 0.02 | 0.03 | − 6.29 | 3.21 × 10−10 | 102,259.78 |
CR026 | Dynactin-associated protein | DYNAP.10692.48.3 | DYNAP | top1 | 1 | 0 | 1 | 0.02 | 0.02 | 6.29 | 3.21 × 10−10 | 3,934.47 |
CCNC | Cyclin-C | CCNC.7817.36.3 | CCNC | top1 | 1 | 0 | 1 | 0.02 | 0.03 | 6.11 | 1.01 × 10−9 | 14,622.63 |
CLC4E | C-type lectin domain family 4 member E | CLEC4E.7077.9.4 | CLEC4E | top1 | 1 | 0 | 1 | 0.02 | 0.02 | 6.11 | 1.01 × 10−9 | 105,033.89 |
CEACAM1 | Carcinoembryonic antigen-related cell adhesion molecule 1 | CEACAM1.8031.11.3 | CEACAM1 | enet | 21 | 0 | 21 | 0.23 | 0.26 | 5.94 | 2.91 × 10−9 | 2,400.48 |
AT1A1 | Sodium/potassium-transporting ATPase subunit alpha-1 | ATP1A1.11993.227.3 | ATP1A1 | enet | 15 | 0 | 15 | 0.06 | 0.07 | 5.91 | 3.52 × 10−9 | 7,027.43 |
CF226 | Uncharacterized protein C6orf226 | C6orf226.8078.15.3 | C6orf226 | lasso | 7 | 0 | 7 | 0.07 | 0.07 | 5.74 | 9.61 × 10−9 | 1,915.81 |
AXIN2 | Axin-2 | AXIN2.8429.16.3 | AXIN2 | enet | 18 | 0 | 18 | 0.40 | 0.44 | 5.57 | 2.48 × 10−8 | 1,978.90 |
TRML4 | Trem-like transcript 4 protein | TREML4.11139.4.3 | TREML4 | lasso | 9 | 0 | 9 | 0.21 | 0.20 | − 5.57 | 2.51 × 10−8 | 253.89 |
DAF | Complement decay-accelerating factor | CD55.5069.9.3 | CD55 | lasso | 11 | 11 | 0 | 0.11 | 0.07 | − 5.57 | 2.55 × 10−8 | 197.03 |
EVI2B | Protein EVI2B | EVI2B.13028.2.3 | EVI2B | enet | 11 | 0 | 11 | 0.07 | 0.05 | − 5.52 | 3.30 × 10−8 | 11,571.33 |
TMIE | Transmembrane inner ear expressed protein | TMIE.7992.3.3 | TMIE | enet | 7 | 0 | 7 | 0.04 | 0.05 | 5.47 | 4.46 × 10−8 | 10,490.88 |
AMBN | Ameloblastin | AMBN.6522.57.3 | AMBN | lasso | 11 | 0 | 11 | 0.15 | 0.07 | − 5.47 | 4.52 × 10−8 | 31,259.13 |
SLAF5 | SLAM family member 5 | CD84.8770.136.3 | CD84 | blup | 46 | 0 | 46 | 0.05 | 0.08 | 5.46 | 4.65 × 10−8 | 644.50 |
SG1C1 | Secretoglobin family 1C member 1 | SCGB1C1.5960.49.3 | SCGB1C1 | enet | 25 | 0 | 25 | 0.18 | 0.10 | − 5.42 | 5.84 × 10−8 | 47,187.26 |
KCNE2 | Potassium voltage-gated channel subfamily E member 2 | KCNE2.10427.2.3 | KCNE2 | enet | 33 | 0 | 33 | 0.26 | 0.26 | − 5.38 | 7.55 × 10−8 | 8,215.37 |
FA20A | Pseudokinase FAM20A | FAM20A.6433.57.3 | FAM20A | enet | 30 | 17 | 13 | 0.04 | 0.03 | − 5.36 | 8.43 × 10−8 | 4,985.48 |
SHSA3 | Protein shisa-3 homolog | SHISA3.7057.18.3 | SHISA3 | enet | 22 | 0 | 22 | 0.23 | 0.16 | − 5.20 | 2.01 × 10−7 | 2,200.66 |
NPTX2 | Neuronal pentraxin-2 | NPTX2.6521.35.3 | NPTX2 | enet | 30 | 0 | 30 | 0.04 | 0.05 | 5.20 | 2.01 × 10−7 | 1,685.45 |
ILT-4 | Leukocyte immunoglobulin-like receptor subfamily B member 2 | LILRB2.5633.65.3 | LILRB2 | lasso | 8 | 6 | 2 | 0.21 | 0.22 | 5.19 | 2.15 × 10−7 | 6.22 |
DIAC | Di-N-acetylchitobiase | CTBS.6115.40.3 | CTBS | enet | 20 | 0 | 20 | 0.14 | 0.09 | − 5.11 | 3.23 × 10−7 | 24,873.14 |
IGFL4 | Insulin growth factor-like family member 4 | IGFL4.6353.60.3 | IGFL4 | enet | 18 | 0 | 18 | 0.10 | 0.05 | − 4.95 | 7.47 × 10−7 | 300.60 |
NAP-2 | Neutrophil-activating peptide 2 | PPBP.2790.54.2 | PPBP | enet | 22 | 0 | 22 | 0.03 | 0.01 | − 4.93 | 8.04 × 10−7 | 34,653.31 |
MCFD2 | Multiple coagulation factor deficiency protein 2 | MCFD2.10476.23.3 | MCFD2 | blup | 744 | 0 | 744 | 0.53 | 0.60 | 4.92 | 8.62 × 10−7 | 9,597.07 |
SLUR1 | Secreted Ly-6/uPAR-related protein 1 | SLURP1.6401.73.3 | SLURP1 | lasso | 4 | 0 | 4 | 0.06 | 0.03 | − 4.86 | 1.17 × 10−6 | 1,285.78 |
SGCB | Beta-sarcoglycan | SGCB.7034.4.3 | SGCB | enet | 16 | 0 | 16 | 0.10 | 0.06 | − 4.84 | 1.30 × 10−6 | 12,688.03 |
RN165 | RING finger protein 165 | RNF165.11561.32.3 | RNF165 | enet | 18 | 0 | 18 | 0.15 | 0.11 | − 4.84 | 1.32 × 10−6 | 12,275.48 |
PSD2 | PH and SEC7 domain-containing protein 2 | PSD2.9118.7.3 | PSD2 | enet | 43 | 0 | 43 | 0.15 | 0.16 | − 4.74 | 2.14 × 10−6 | 11,257.00 |
ICOS | Inducible T-cell costimulator | ICOS.14084.191.3 | ICOS | enet | 27 | 0 | 27 | 0.17 | 0.12 | − 4.72 | 2.41 × 10−6 | 1,058.05 |
SHPS1 | Tyrosine-protein phosphatase non-receptor type substrate 1 | SIRPA.5430.66.3 | SIRPA | blup | 2,563 | 2,506 | 57 | 0.63 | 0.62 | 4.63 | 3.71 × 10−06 | 1,480.84 |
FKBP6 | Inactive peptidyl-prolyl cis–trans isomerase FKBP6 | FKBP6.12529.32.3 | FKBP6 | blup | 1,593 | 0 | 1,593 | 0.49 | 0.53 | 4.54 | 5.53 × 10−6 | 17,800.84 |
Cathepsin H | Cathepsin H | CTSH.8465.52.3 | CTSH | lasso | 13 | 12 | 1 | 0.30 | 0.28 | 4.51 | 6.58 × 10−6 | 15.80 |
Siglec-3 | Myeloid cell surface antigen CD33 | CD33.3166.92.1 | CD33 | enet | 98 | 92 | 6 | 0.41 | 0.45 | 4.47 | 7.78 × 10−6 | 0.37 |
SPA9 | Serpin A9 | SERPINA9.7266.4.3 | SERPINA9 | lasso | 4 | 0 | 4 | 0.02 | 0.02 | 4.46 | 8.02 × 10−6 | 1,990.20 |
B3GN1 | Beta-1,4-glucuronyltransferase 1 | B3GNT1.8259.25.3 | B3GNT1 | enet | 50 | 0 | 50 | 0.15 | 0.17 | 4.40 | 1.09 × 10−5 | 6,090.90 |
APBB2 | Amyloid beta A4 precursor protein-binding family B member 2 | APBB2.12761.12.3 | APBB2 | lasso | 9 | 6 | 3 | 0.03 | 0.01 | 4.24 | 2.26 × 10−5 | 613.20 |
TMM85 | ER membrane protein complex subunit 4 | EMC4.13516.46.3 | EMC4 | enet | 73 | 0 | 73 | 0.21 | 0.20 | − 4.20 | 2.63 × 10−5 | 24,505.40 |
Siglec-9 | Sialic acid-binding Ig-like lectin 9 | SIGLEC9.3007.7.2 | SIGLEC9 | blup | 618 | 580 | 38 | 0.72 | 0.73 | 4.19 | 2.75 × 10−5 | 99.83 |
ADSV | Adseverin | SCIN.12684.5.3 | SCIN | lasso | 4 | 0 | 4 | 0.03 | 0.02 | 4.17 | 3.01 × 10−5 | 340.75 |