Background
Methods
Protein-protein interaction analysis
Pathway analyses
Input for protein-protein interaction and pathway analyses
Autoantibody targets (n = 28) | SNPs (n = 22) | |||||
---|---|---|---|---|---|---|
Symbol | Description | MSA/MAA | rsID | Coordinates (GRCh37 assembly) | Immunochip p value [9] | Clinical group |
GARS
|
Glycyl-tRNA synthetase
|
Anti-EJ
|
rs5754467
| Chr22:21985094 | 4.67 × 10-07
| IIM |
YARS
|
Tyrosyl-tRNA synthetase
|
Anti-Ha
|
rs6599390
| Chr4:956047 | 6.48 × 10-07
| IIM |
HARS
|
Histidyl-tRNA synthetase
|
Anti-Jo-1
|
rs4853540
| Chr2:191917317 | 1.57 × 10-06
| IIM |
NARS
|
Asparaginyl-tRNA synthetase
|
Anti-KS
|
rs10189330
| Chr2:99389870 | 2.68 × 10-06
| IIM |
IARS
|
Isoleucyl-tRNA synthetase
|
Anti-OJ
|
rs570676
| Chr11:36492191 | 9.42 × 10-06
| IIM |
AARS
|
Alanyl-tRNA synthetase
|
Anti-PL-12
|
rs223900
| Chr16:57445376 | 9.97 × 10-06
| IIM |
TARS
|
Threonyl-tRNA synthetase
|
Anti-PL-7
|
rs451375
(Proxy for rs376072) | Chr3:28049889 | (1.45 × 10-05) | IIM |
FARSA | Phenylalanyl-tRNA synthetase, alpha subunit | Anti-Zo-α |
rs3116494
| Chr2:204592021 | 1.54 × 10-05
| IIM |
FARSB
|
Phenylalanyl-tRNA synthetase, beta subunit
|
Anti-Zo-β
|
rs11064180
| Chr12:6523249 | 1.61 × 10-05
| IIM |
CHD3 | Chromodomain helicase DNA binding protein 3 | Anti-Mi-2α |
rs2476601
| Chr1:114377568 | 7.22 × 10-09/7.90 × 10-11
| IIM/PM |
CHD4
a
|
Chromodomain helicase DNA binding protein 4
|
Anti-Mi-2β
| rs3094013 | Chr6:31434366 | 6.36 × 10-76
| PM |
SRP54
|
Signal recognition particle 54 kDa
|
Anti-SRP
|
rs9905921
| Chr17:71527243 | 2.01 × 10-06
| PM |
SAE1 | Small ubiquitin related modifier 1 activating enzyme subunit 1 | Anti-SAE-1 |
rs7956536
| Chr12:109980516 | 3.66 × 10-06
| PM |
UBA2
|
Ubiquitin-like modifier activating enzyme 2
|
Anti-SAE-2
| rs2286896 | Chr2:191535576 | 3.76 × 10-06
| PM |
TRIM33
|
Tripartite motif containing 33
|
Anti-TIF1γ
|
rs17799348
| Chr8:11333521 | 4.13 × 10-06
| PM |
TRIM24 | Tripartite motif containing 24 | Anti-TIF1α |
rs917998
(Proxy for rs1420095) | Chr2:103068156 | (6.16 × 10-06) | PM |
TRIM28 | Tripartite motif containing 28 | Anti-TIF1β | rs4690220 (Proxy rs11724804 in GRAIL) | Chr4:980464 | 7.47 × 10-06
| PM |
IFIH1
|
Interferon induced with helicase C domain 1
|
Anti-MDA5
|
rs7535818
(Proxy rs2984920 in GRAIL) | Chr1:192545099 | 1.37 × 10-05
| PM |
NT5C1A
|
5'-nucleotidase, cytosolic 1A
| Anti-NT5C1A |
rs3129927
| Chr6:32333827 | 3.74 × 10-48/2.06 × 10-129
| DM/JDM/IIM |
ABTB1
|
Ankyrin repeat and BTB (POZ) domain containing 1
|
Anti-Fer
|
rs4702698
| Chr5:10517908 | 4.77 × 10-06
| DM/JDM |
HMGCR
|
3-hydroxy-3-methylglutaryl-CoA reductase
|
Anti-HMGCR
|
rs4921293
| Chr5:159928876 | 8.27 × 10-06
| DM/JDM |
MORC3
|
MORC family CW-type zinc finger 3
|
Anti-NXP2
|
rs1008723
| Chr17:38066267 | 9.05 × 10-06
| DM/JDM |
PMS1
|
Postmeiotic segregation increased 1
|
Anti-PMS1
| ||||
PMS2 | Postmeiotic segregation increased 2 | Anti-PMS2 | ||||
MLH1
|
MutL homolog 1
|
Anti-MLH1
| ||||
PRKDC
|
Protein kinase, DNA-activated, catalytic polypeptide
|
Anti-DNA PKCS
| ||||
EXOSC9 | Exosome component 9 | Anti-PMScl-75 | ||||
EXOSC10
|
Exosome component 10
|
Anti-PMScl-100
|
Results
Protein-protein interaction analysis identifies significant direct and indirect connectivity
All MSA/MAA targets (n = 28) | Subset of MSA/MAA targetsa (n = 21) | All SNPs (n = 22) | All SNPs (n = 22) and subsets of MSA/MAA targetsa (n = 21) | ||||
---|---|---|---|---|---|---|---|
Gene |
P
corr value | Gene |
P
corr value | Gene |
P
corr value | Gene |
P
corr value |
UBA2 | 3.03 × 10-4
| GARS | 3.16 × 10-4
| UBE3B | 8.03 × 10-4
| TRAF6 | 3.01 × 10-4
|
GARS | 5.05 × 10-4
| PMS1 | 4.21 × 10-4
| TRAF6 | 2.11 × 10-3
| UBE3B | 4.01 × 10-4
|
PMS1 | 3.63 × 10-3
| UBA2 | 3.47 × 10-3
| GARS | 1.20 × 10-3
| ||
TRIM24 | 4.74 × 10-3
| IARS | 5.68 × 10-3
| TARS | 3.90 × 10-3
| ||
YARS | 8.37 × 10-3
| YARS | 1.09 × 10-2
| PSMD3 | 6.99 × 10-3
| ||
TRIM28 | 8.97 × 10-3
| HARS | 1.15 × 10-2
| UBA2 | 1.19 × 10-2
| ||
NARS | 9.17 × 10-3
| AARS | 1.78 × 10-2
| PMS1 | 1.67 × 10-2
| ||
TRIM33 | 1.10 × 10-2
| NARS | 3.23 × 10-2
| HSPA1B | 2.73 × 10-2
| ||
IARS | 1.15 × 10-2
| YARS | 3.79 × 10-2
| ||||
MLH1 | 1.79 × 10-2
| IARS | 3.98 × 10-2
| ||||
HARS | 1.95 × 10-2
| HARS | 4.61 × 10-2
| ||||
CHD3 | 2.67 × 10-2
| HSPA1A | 4.94 × 10-2
| ||||
FARSA | 3.02 × 10-2
| ||||||
AARS | 3.10 × 10-2
| ||||||
TARS | 3.23 × 10-2
| ||||||
EXOSC9 | 3.43 × 10-2
| ||||||
FARSB | 4.61 × 10-2
|