Table 1.
Non-HLA genetic associations with rheumatoid arthritis by December 2021
| SNP1 | Chromosome: position2 | Gene/Locus | OR | 95%CI | Immune function | ACPA | Population3 | Reference |
|---|---|---|---|---|---|---|---|---|
| rs2843401, rs3890745, rs2258734 | 1:2596694 | MMEL1 | 0.91 | (0.89–0.93) | - | Positive | Asians, Europeans | [46, 50, 51] |
| rs227163 | 1:7901146 | TNFRSF9 | 1.04 | (1.02–1.06) | Yes | Combined | Asians | [6] |
| rs2240336, rs2301888, esv3585367 | 1:17347907 | PADI4 | 0.88 | (0.86–0.90) | Yes | Combined | Asians, Europeans | [8, 46, 50] |
| rs28411352 | 1:37812907 | MTF1 | 1.10 | (1.07–1.13) | - | Combined | Europeans, Trans Meta | [6] |
| rs883220, rs7540342 | 1:38151199 | POU3F1 | 0.89 | (0.86–0.92) | - | Positive | Europeans | [8, 46] |
| rs41269479 | 1:41701111 | HIVEP3 | 1.15 | (1.09–1.20) | Yes | Positive | Asians | [8] |
| rs4655698 | 1:67332644 | IL12RB2 | 1.09 | (1.05–1.11) | Yes | Positive | Trans Meta | [8] |
| rs41313373 | 1:92474854 | GFI1 | 1.12 | (1.08–1.16) | Yes | Positive | Europeans, Trans Meta | [8] |
| rs2476601 | 1:113834946 | PTPN22 | 1.81 | (1.73–1.89) | Yes | Positive | Europeans | [43, 52] |
| rs11586238, rs798000, rs624988 | 1:116720516 | CD2 | 1.12 | (1.09–1.16) | Yes | Positive | Europeans | [8, 51] |
| rs2228145, rs12126142 | 1:154454494 | IL6R | 0.93 | (0.91–0.95) | Yes | Combined | Europeans, Trans Meta | [6, 7, 46] |
| rs2317230, rs2317231 | 1:157705207 | FCRL3 | 1.08 | (1.05–1.10) | Yes | Positive | Trans Meta | [6] |
| rs12026490 | 1:160447367 | SLAMF6 | 0.80 | (0.75–0.85) | Yes | Combined | Asians | [7] |
| rs3753389 | 1:160837363 | CD244 | 1.30 | (1.18–1.43) | Yes | Combined | Asians | [53] |
| rs10917571 | 1:161549621 | FCGR3A | 0.91 | (0.89–0.94) | Yes | Positive | Trans Meta | [8] |
| rs2105325, rs61828284, rs6681482 | 1:173380586 | TNFSF4 | 1.12 | (1.08–1.15) | Yes | Combined | Europeans, Trans Meta | [6, 8, 57] |
| rs10911902, rs12145329 | 1:186663185 | PTGS2 | 0.92 | (0.89–0.95) | Yes | Positive | Trans Meta | [7, 8] |
| rs28398409 | 1:198614892 | PTPRC | 0.91 | (0.88–0.94) | Yes | Combined | Trans Meta | [8] |
| rs762574969 | 1:235637057 | GNG4 | 0.91 | (0.88–0.94) | - | Combined | Europeans | [8] |
| rs10175798 | 2:30226728 | LBH | 0.92 | (0.90–0.94) | Yes | Combined | Europeans, Trans Meta | [6] |
| rs34695944, rs13031237 | 2:60897715 | REL | 1.12 | (1.08–1.15) | Yes | Positive | Europeans | [6, 47] |
| rs11900673 | 2:62225526 | B3GNT2 | 1.15 | (1.08–1.21) | Yes | Combined | Asians | [50] |
| rs6546146, rs934734, rs1858037 | 2:65329190 | SPRED2 | 0.90 | (0.88–0.93) | Yes | Positive | Asians, Europeans | [50, 52] |
| rs143259280 | 2:69982037 | PCBP1-AS1 | 1.09 | (1.06–1.12) | - | Positive | Trans Meta | [8] |
| rs6705628 | 2:73981235 | DGUOK-AS1 | 0.88 | (0.85–0.92) | - | Combined | Asians | [7] |
| rs10209110, rs12712065 | 2:100056230 | AFF3 | 1.10 | (1.08–1.13) | Yes | Combined | Asians, Europeans | [8, 46, 52] |
| rs6732565 | 2:110850255 | ACOXL | 1.07 | (1.05–1.10) | - | Combined | Europeans, Trans Meta | [6, 8] |
| rs13426947, rs7574865 | 2:191068528 | STAT4 | 1.16 | (1.13–1.19) | Yes | Combined | Asians, Europeans | [46, 50] |
| rs10497813 | 2:198049348 | PLCL1-LINC01923 | 1.06 | (1.04–1.09) | - | Combined | Europeans, Trans Meta | [8, 58] |
| rs6715284, rs2141331 | 2:201289674 | CASP8 | 1.15 | (1.10–1.20) | Yes | Combined | Europeans, Trans Meta | [6, 8] |
| rs1980422 | 2:203745673 | CD28 | 1.12 | (1.09–1.16) | Yes | Combined | Europeans | [51] |
| rs11571302, rs3087243 | 2:203878211 | CTLA4 | 0.88 | (0.86–0.90) | Yes | Positive | Asians, Europeans | [8, 52] |
| rs77574423 | 3:11943270 | TAMM41-SYN2 | 0.89 | (0.86–0.93) | - | Positive | Europeans | [8] |
| rs4452313, rs4602367 | 3:17005540 | PLCL2 | 0.93 | (0.91–0.95) | Yes | Combined | Europeans, Trans Meta | [6, 7] |
| rs3806624 | 3:27723132 | EOMES | 0.92 | (0.89–0.94) | Yes | Combined | Europeans, Trans Meta | [6, 7] |
| rs73081554 | 3:58317208 | DNASE1L3 | 1.18 | (1.11–1.25) | Yes | Combined | Europeans | [6] |
| rs62264113 | 3:127573490 | TPRA1 | 0.92 | (0.89–0.95) | - | Combined | Trans Meta | [8] |
| rs9826828 | 3:136683218 | IL20RB | 1.44 | (1.28–1.61) | Yes | Combined | Europeans | [6] |
| rs4687070 | 3:189588861 | TPRG1-TP63 | 1.15 | (1.09–1.20) | - | Combined | Trans Meta | [8] |
| rs4690029 | 4:2721088 | FAM193A | 0.94 | (0.92–0.96) | - | Combined | Trans Meta | [8] |
| rs13142500, rs13103285 | 4:10725733 | CLNK | 1.10 | (1.08–1.13) | Yes | Combined | Asians, Trans Meta | [6, 7] |
| rs932036, rs874040, rs11933540 | 4:26089240 | RBPJ | 1.15 | (1.11–1.19) | Yes | Combined | Europeans | [6, 46, 52] |
| rs2664035 | 4:48218822 | TEC | 1.07 | (1.04–1.10) | Yes | Combined | Europeans | [6] |
| rs2867461 | 4:78592061 | ANXA3 | 1.13 | (1.09–1.17) | Yes | Combined | Asians | [50] |
| rs950918814 | 4:80031255 | ANTXR2 | 0.93 | (0.91–0.95) | - | Combined | Trans Meta | [8] |
| rs58107865 | 4:108140462 | LEF1 | 0.84 | (0.80–0.88) | Yes | Combined | Asians | [8] |
| rs6814280 | 4:122122507 | KIAA1109 | 0.93 | (0.90–0.96) | - | Positive | Europeans | [8] |
| rs2918392 | 5:10704685 | DAP | 0.94 | (0.91–0.96) | Yes | Combined | Trans Meta, Europeans | [7, 8] |
| rs56787183 | 5:40499188 | PTGER4 | 0.85 | (0.80–0.90) | Yes | Combined | Trans Meta | [8] |
| rs71624119, rs6859212, rs7731626 | 5:56144903 | ANKRD55 | 0.82 | (0.79–0.85) | Yes | Combined | Asians, Europeans | [7, 8, 46, 52] |
| rs71624119, rs7731626 | 5:56144903 | ANKRD55 | 0.85 | (0.80–0.91) | Yes | Negative | Europeans | [8, 46] |
| rs2561477, rs403214, rs187579 | 5:103273223 | MACIR | 1.10 | (1.06–1.13) | Yes | Combined | Europeans, Trans Meta | [6–8, 52] |
| rs657075, rs244685 | 5:132094425 | CSF2 | 1.09 | (1.06–1.12) | Yes | Combined | Asians, Trans Meta | [7, 50] |
| rs244468 | 5:143224856 | ARHGAP26 | 0.93 | (0.91–0.95) | - | Combined | Trans Meta | [8] |
| rs1422673 | 5:151059427 | TNIP1 | 1.10 | (1.06–1.14) | Yes | Positive | Europeans | [8] |
| rs9378815, rs6930468 | 6:426155 | IRF4 | 0.91 | (0.89–0.94) | Yes | Combined | Trans Meta | [6, 8] |
| rs12529514, rs12530098 | 6:14096427 | CD83 | 1.15 | (1.10–1.20) | Yes | Combined | Asians, Trans Meta | [7, 50] |
| rs113532504 | 6:15195451 | JARID2 | 1.13 | (1.08–1.18) | Yes | Combined | Europeans | [8] |
| rs67318457 | 6:23924793 | NRSN1 | 1.09 | (1.05–1.12) | - | Positive | Europeans | [8] |
| rs2234067, rs11420145 | 6:36387877 | ETV7 | 1.15 | (1.10–1.20) | Yes | Combined | Europeans, Trans Meta | [6, 8] |
| rs2233424, rs28362855 | 6:44266184 | POLR1C, NFKBE | 1.22 | (1.17–1.26) | Yes | Combined | Asians, Europeans | [6, 8, 50] |
| rs72928038 | 6:90267049 | BACH2 | 1.09 | (1.06–1.11) | Yes | Combined | Europeans, Trans Meta | [8, 23, 59] |
| rs548234, rs9372120, rs3804333 | 6:106120159 | PRDM1-ATG5 | 1.11 | (1.07–1.15) | Yes | Positive | Asians, Europeans | [6, 8, 51] |
| rs10499194, rs6920220, rs6932056, rs7752903 | 6:137681500 | TNFAIP3 | 1.33 | (1.26–1.40) | Yes | Positive | Asians, Europeans | [6, 46, 50, 60] |
| rs9373594 | 6:149513438 | PPIL4 | 1.09 | (1.06–1.12) | Yes | Combined | Asians | [6] |
| rs629326, rs2451258 | 6:159075681 | TAGAP | 1.11 | (1.08–1.14) | Yes | Positive | Europeans | [6, 46] |
| rs59466457, rs3093023, rs1571878 | 6:167124266 | CCR6 | 0.86 | (0.84–0.88) | Yes | Positive | Asians, Europeans | [46, 50, 52] |
| rs940825 | 7:17167540 | AGR3-AHR | 1.13 | (1.08–1.18) | - | Positive | Europeans | [8] |
| rs182199544 | 7:27044962 | SKAP2-HOXA1 | 0.87 | (0.84–0.91) | Yes | Positive | Europeans | [8] |
| rs67250450, rs740122 | 7:28135367 | JAZF1 | 0.92 | (0.90–0.95) | - | Combined | Europeans, Trans Meta | [6, 7] |
| rs6583441 | 7:50322278 | IKZF1 | 0.95 | (0.93–0.97) | Yes | Combined | Trans Meta | [8] |
| rs113066392, rs73366469 | 7:74611832 | GTF2IRD1-NCF1 | 1.43 | (1.33–1.55) | Yes | Combined | Asians | [7, 56, 61] |
| rs4272, rs42044 | 7:92607515 | CDK6 | 0.92 | (0.89–0.94) | Yes | Combined | Europeans, Trans Meta | [6, 8] |
| rs6979218 | 7:100295525 | CASTOR3-SPDYE3 | 0.92 | (0.89–0.94) | - | Combined | Europeans, Trans Meta | [8] |
| rs3807306, rs10488631 | 7:128940626 | IRF5 | 0.88 | (0.86–0.91) | Yes | Combined | Asians, Europeans | [46, 50, 52] |
| rs4840565, rs2736340 | 8:11488036 | BLK | 1.12 | (1.09–1.15) | Yes | Combined | Asians, Europeans | [6–8, 47] |
| rs998731, rs10453119 | 8:80183160 | TPD52 | 1.08 | (1.05–1.11) | - | Combined | Europeans, Trans Meta | [6, 8] |
| rs678347, rs1264600 | 8:101451374 | GRHL2 | 1.08 | (1.05–1.11) | - | Combined | Europeans, Trans Meta | [6, 8] |
| rs1516971, rs16903108 | 8:128529854 | PVT1 | 1.15 | (1.10–1.20) | - | Combined | Europeans, Trans Meta | [6, 8] |
| rs11777380 | 8:133199722 | CCN4 | 0.92 | (0.90–0.95) | - | Combined | Trans Meta | [8] |
| rs911760 | 9:5438435 | PLGRKT | 1.15 | (1.09–1.20) | - | Positive | Europeans | [8] |
| rs2812378, rs11574914 | 9:34710263 | CCL21 | 1.12 | (1.09–1.16) | Yes | Positive | Europeans, Trans Meta | [6, 8, 46, 52] |
| rs3761847, rs10985070 | 9:120927961 | TRAF1-C5 | 0.92 | (0.90–0.95) | Yes | Positive | Europeans, Trans Meta | [5, 6] |
| rs706778, rs3134883 | 10:6056986 | IL2RA | 1.10 | (1.08–1.13) | Yes | Combined | Europeans, Trans Meta | [6, 7, 52] |
| rs947474, rs502919 | 10:6348488 | PRKCQ | 0.92 | (0.90–0.94) | Yes | Combined | Europeans, Trans Meta | [6, 7] |
| rs2275806, rs3824660, rs10905284 | 10:8053377 | GATA3 | 0.93 | (0.91–0.95) | Yes | Positive | Europeans, Trans Meta | [6, 8, 46] |
| rs793108, rs793095, rs1538981 | 10:31126177 | ZNF438 | 1.07 | (1.05–1.09) | - | Combined | Trans Meta | [6–8] |
| rs2671692, rs7097397 | 10:48889774 | WDFY4 | 0.92 | (0.90–0.94) | Yes | Combined | Asians, Trans Meta | [6–8] |
| rs12764378, rs10821944, rs7902146 | 10:62040245 | ARID5B | 1.16 | (1.13–1.19) | Yes | Positive | Asians, Europeans | [8, 46, 50] |
| rs6479800, rs3125734 | 10:62277122 | RTKN2 | 1.11 | (1.07–1.15) | - | Combined | Asians, Trans Meta | [6, 49] |
| rs726288 | 10:79947217 | SFTPD | 1.14 | (1.07–1.20) | Yes | Combined | Asians | [6] |
| rs734094 | 11:2301990 | TSPAN32 | 1.08 | (1.05–1.10) | Yes | Positive | Trans Meta | [8] |
| rs9943599 | 11:9731194 | SWAP70 | 1.09 | (1.06–1.11) | Yes | Combined | Asians, Trans Meta | [7, 48] |
| rs595158, rs968567, rs7943728 | 11:61142109 | FADS1-FADS2-FADS3 | 1.12 | (1.07–1.16) | - | Combined | Europeans | [6, 8, 46] |
| rs660442, rs479777 | 11:64275525 | BAD | 0.90 | (0.87–0.93) | Yes | Combined | Asians, Trans Meta | [7, 8] |
| rs59578717 | 11:69092402 | TPCN2 | 0.91 | (0.88–0.94) | - | Combined | Asians | [7] |
| rs3781913, rs79145843 | 11:72662452 | PDE2A-ARAP1 | 0.88 | (0.84–0.91) | Yes | Combined | Asians, Trans Meta | [7, 8, 50] |
| rs4409785 | 11:95578258 | CEP57 | 0.91 | (0.88–0.94) | - | Combined | Europeans, Trans Meta | [6, 7] |
| rs138193887 | 11:108096623 | CUL5 | 1.21 | (1.13–1.29) | - | Combined | Europeans | [6] |
| rs10892279, rs4938573, rs73005423 | 11:118741072 | DDX6 | 1.15 | (1.09–1.22) | - | Positive | Asians, Europeans | [8, 46, 50] |
| rs10790268 | 11:118858682 | CXCR5 | 0.87 | (0.84–0.90) | Yes | Combined | Europeans | [6] |
| rs12795702 | 11:128286419 | LOC107984408 | 1.09 | (1.06–1.12) | - | Combined | Trans Meta | [7] |
| rs73013527, rs10556591 | 11:128627057 | FLI1-ETS1 | 0.92 | (0.90–0.95) | Yes | Combined | Trans Meta | [6, 8] |
| rs4963581 | 12:24660347 | LOC105369698 | 1.09 | (1.06–1.12) | - | Combined | Trans Meta | [7] |
| rs1427749 | 12:45976333 | SCAF11 | 1.08 | (1.05–1.11) | Yes | Combined | Trans Meta | [8] |
| rs773125, rs4622308, rs705700 | 12:56001170 | CDK2 | 1.09 | (1.07–1.12) | Yes | Combined | Europeans, Trans Meta | [6, 7] |
| rs10683701, rs1696466 | 12:57698305 | OS9-AGAP2 | 1.06 | (1.04–1.08) | - | Positive | Europeans, Trans Meta | [8, 46] |
| rs10774624, rs77465633, rs3184504 | 12:111395984 | SH2B3-PTPN11 | 1.32 | (1.20–1.45) | Yes | Combined | Asians, Europeans | [6, 7] |
| rs61944750 | 13:28060796 | FLT3 | 0.91 | (0.88–0.94) | Yes | Combined | Trans Meta | [8] |
| rs9603616, rs9532434 | 13:39793932 | COG6 | 0.89 | (0.87–0.91) | - | Combined | Asians, Europeans | [6, 7] |
| rs2147161 | 13:42408166 | AKAP11-LINC02341 | 1.10 | (1.06–1.13) | - | Positive | Europeans | [8] |
| rs9557321 | 13:99868847 | CLYBL | 1.73 | (1.42–2.11)* | - | Negative | Europeans | [34] |
| rs3783782, rs146492555 | 14:61473957 | PRKCH | 1.14 | (1.09–1.18) | - | Combined | Asians, Trans Meta | [6, 8] |
| rs1950897, rs1885013 | 14:68293424 | RAD51B | 1.11 | (1.08–1.14) | - | Combined | Asians, Europeans | [6, 7] |
| rs3825568 | 14:68793871 | ZFP36L1 | 1.08 | (1.06–1.11) | - | Combined | Asians, Trans Meta | [7, 48] |
| rs175714 | 14:75515513 | BATF | 0.94 | (0.92–0.96) | Yes | Combined | Trans Meta | [8] |
| rs2841277, rs2582532, rs3001423 | 14:104924668 | PLD4 | 0.85 | (0.82–0.88) | - | Combined | Asians | [6, 8, 50] |
| rs8043085, rs8032939, rs6495979 | 15:38535939 | RASGRP1 | 0.88 | (0.86–0.90) | Yes | Positive | Asians, Europeans | [6–8, 46] |
| rs8026898 | 15:69699078 | TLE3 | 1.14 | (1.11–1.17) | Yes | Combined | Europeans, Trans Meta | [8, 46] |
| rs115284761 | 15:77034495 | PSTPIP1 | 0.91 | (0.89–0.94) | Yes | Combined | Europeans, Trans Meta | [8] |
| rs199894206, rs7171617 | 15:90495653 | IQGAP1 | 1.12 | (1.08–1.16) | - | Combined | Asians, Trans Meta | [7, 8] |
| rs4780401, rs7206670, rs4584833 | 16:11745470 | TXNDC11 | 1.07 | (1.05–1.10) | - | Combined | Europeans, Trans Meta | [6, 7] |
| rs149041927 | 16:23859897 | PRKCB | 0.91 | (0.88–0.94) | Yes | Combined | Asians | [7] |
| rs12918327, rs34480360 | 16:30615295 | ZNF689 | 1.09 | (1.06–1.12) | - | Combined | Trans Meta | [7, 8] |
| rs13330176, rs9927316 | 16:85985481 | IRF8 | 0.91 | (0.89–0.94) | Yes | Positive | Asians, Europeans | [6–8, 46] |
| rs72634030, rs8073171 | 17:5369285 | C1QBP | 1.12 | (1.08–1.17) | Yes | Combined | Trans Meta | [6, 8] |
| rs11375064 | 17:27577049 | KSR1 | 0.93 | (0.90–0.95) | - | Positive | Trans Meta | [8] |
| rs1877030 | 17:39583908 | MED1 | 1.09 | (1.06–1.12) | - | Combined | Trans Meta | [6] |
| rs2305480, rs2872507, rs56750287 | 17:39905943 | GSDMB | 0.93 | (0.91–0.95) | Yes | Combined | Europeans, Trans Meta | [6, 8, 46] |
| rs591549 | 18:3542249 | DLGAP1 | 0.91 | (0.88–0.94) | - | Combined | Trans Meta | [8] |
| rs2847297, rs8083786, rs7241016 | 18:12797695 | PTPN2 | 0.91 | (0.89–0.94) | Yes | Combined | Asians, Europeans | [6, 8, 50] |
| rs866205108 | 18:62342401 | TNFRSF11A | 1.10 | (1.06–1.14) | Yes | Positive | Trans Meta | [8] |
| rs2469434, rs143107126 | 18:69876810 | CD226 | 1.07 | (1.05–1.10) | Yes | Combined | Asians, Trans Meta | [6, 8] |
| rs1943199 | 18:75750899 | LINC01898 | 1.94 | (1.54–2.44)* | - | Negative | Europeans | [34] |
| rs10415976 | 19:941603 | ARID3A | 0.92 | (0.90–0.95) | - | Combined | Trans Meta | [8] |
| rs34536443 | 19:10352442 | TYK2 | 0.68 | (0.62–0.75) | Yes | Positive | Europeans | [46] |
| rs147622113 | 19:10661265 | ILF3 | 0.68 | (0.60–0.77) | Yes | Combined | Europeans | [6] |
| rs55762233 | 19:19256510 | HAPLN4 | 1.10 | (1.07–1.14) | - | Combined | Trans Meta | [8] |
| rs28373672 | 19:35722170 | KMT2B | 0.93 | (0.91–0.96) | - | Combined | Trans Meta | [8] |
| rs8106598 | 19:51514686 | SIGLEC6 | 1.08 | (1.05–1.11) | - | Positive | Trans Meta | [8] |
| rs6032662, rs4810485, rs1883832 | 20:46105671 | CD40 | 0.90 | (0.88–0.92) | Yes | Positive | Asians, Europeans | [6, 8, 46, 51] |
| rs6011186, rs4809371 | 20:63852655 | C20orf181 | 0.90 | (0.87–0.93) | - | Combined | Asians, Trans Meta | [7, 8] |
| rs73194058, rs8126756, rs2300373 | 21:33391982 | IFNGR2 | 1.09 | (1.06–1.12) | Yes | Combined | Europeans, Trans Meta | [6–8] |
| rs9979383, rs8133843, rs66922517 | 21:35343463 | RUNX1 | 1.08 | (1.06–1.11) | Yes | Combined | Europeans, Trans Meta | [6–8, 46] |
| rs1893592 | 21:42434957 | UBASH3A | 1.10 | (1.07–1.13) | Yes | Combined | Europeans, Trans Meta | [6] |
| rs2075876, rs7278257, rs11454989 | 21:44289270 | AIRE | 0.91 | (0.89–0.94) | Yes | Combined | Asians, Trans Meta | [7, 8, 54] |
| rs11089637, rs5754104 | 22:21624807 | UBE2L3-YDJC | 1.09 | (1.06–1.12) | Yes | Combined | Europeans, Trans Meta | [6–8] |
| rs5756407 | 22:36920217 | CSF2RB-LOC105373023 | 1.06 | (1.04–1.08) | Yes | Combined | Trans Meta | [8] |
| rs909685, rs2069235 | 22:39351666 | SYNGR1 | 1.14 | (1.11–1.17) | - | Combined | Asians, Europeans | [6, 7] |
| rs35156883 | 22:45350272 | SMC1B | 1.10 | (1.06–1.13) | - | Combined | Asians | [7] |
| rs201408742, rs6619397, rs74842123 | X:79209119 | GPR174-KIF4CP | 1.11 | (1.08–1.15) | Yes | Combined | Asians, Trans Meta | [6–8] |
| rs13397, rs5987194 | X:153982797 | IRAK1 | 1.15 | (1.12–1.18) | Yes | Positive | Asians, Europeans | [6, 7, 46] |
1Genetic variation with genome-wide significance for association
2Position is indicated for the first variation in the list
3Trans Meta – meta-analysis for populations with European and Asian ancestry
OR odds ratio, 95%CI 95% confidence interval for OR, ACPA anti-citrullinated peptide/protein antibodies