Table 1.
Myositis-specific and associated autoantibody targets and significant or suggestive SNPs used in 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 | ||||
Single nucleotide polymorphisms (SNPs) were included if they reached the suggestive significance threshold (p < 2.25 × 10-5) for association with idiopathic inflammatory myopathies (IIM) in the Immunochip study published by Rothwell et al., 2015. Subset of autoantibody targets used in Disease Association Protein-Protein Link Evaluator (DAPPLE) formed by selecting one protein from each complex are shown in bold (n = 21). Subset of SNPs used in Gene Relationships Across Implicated Loci (GRAIL) analysis due to overlapping regions also shown in bold (n = 19) and proxies used for unrecognised SNPs are in brackets. aCHD4 also not included in GRAIL analysis due to overlapping regions (autoantibody targets = 27). Clinical groups included polymyositis (PM), adult/juvenile dermatomyositis (DM/JDM) and all sub-groups combined (IIM)