Fine mapping on a Immunochip  (Illumina Infinium) custom SNP array, in 11,475 individuals with rheumatoid arthritis (cases) and 15,870 controls of European ancestry for 129,464 markers. The analyzed data was combined in a meta-analysis with GWAS data from additional independent 2,363 cases and 17,872 controls. Genotype calling was performed on all samples using the Genotyping Module (v1.8.4) of the GenomeStudio Data Analysis software package. Initial genotype clustering was performed using the GenTrain2 clustering algorithm. Principal Component Analysis (PCA) was performed using EIGENSOFT (v4.2) with HapMap Phase 2 samples. For relatedness analysis, PLINK (v1.07) and the PCA SNP set was used to calculate identity-by-descent. Genotype data were phased using the SHAPEIT algorithm. Imputation was carried out with IMPUTE and haplotype-phased HapMap Phase 2 European CEU founders as a reference panel. SNPTEST (v2.2) was used to conduct the logistic regression analysis. The meta-analysis and heterogeneity statistics computations were adapted from the MANTEL program.

The study identifies 14 new rheumatoid arthritis (RA) susceptibility loci, for populations of European ancestry, at genome-wide levels of significance (P < 5 X 10-8). Out of  the 14 loci, 7 were identified with ImmunoChip data alone and a further 7, when ImmunoChip data were combined with the GWAS meta-analysis data.
Study Type
Case-Control Study
Exclusion Criteria
Samples were excluded due to :-
  • Call frequency < 99%
  • Failed Autosomal Heterozygosity 
  • Failed PCA (identified as outliers on the basis of ethnicity)
  • Failed IBD (identity-by-descent)
Markers were excluded due to :-
  • Low cluster separation (< 0.4)
  • Low call frequency (< 0.98)
  • Mapped to Y chromosome
  • Mapped to Mitochondrial DNA
  • Monomorphic
  • Illumina default exclusions (zeroed in the default Illumina cluster file)
  • Duplication
For meta-analysis, further SNPs were excluded from each of the datasets due to :- 
  • Low call rate < 0.99 (cases or controls)
  • MAF < 0.01
  • Deviation from Hardy-Weinberg equilibrium, (PHWE < 5.7 × 10-7)


Study Association

RegionLocationGene(s)MarkerAlleleMAFP ValueOdds Ratio
1p13.1chr1:116681530-116755112CD2  rs798000A > G0.3406.20e-06C1.11C
1p13.2chr1:113296527-114009223PTPN22  rs2476601G > A0.0907.50e-77C1.78C
1p34.3chr1:38136523-38238517POU3F1  rs883220C > A0.2602.10e-08C1.12C
1p36.13chr1:17240113-17353103PADI4  rs2240336C > T0.4205.90e-09C1.14C
1p36.32chr1:2431888-2879054MMEL1  rs2843401C > T0.3306.60e-09C1.15C
1q21.3chr1:154335188-154679688IL6R  rs2228145A > C0.4201.30e-08C1.11C
1q23.3chr1:161418623-161665900FCGR2A  rs10494360G > A0.1203.00e-05C1.14C
1q32.1chr1:198626679-199089764PTPRC  rs2014863T > C0.3602.10e-05C1.09C
2p14chr2:65165964-65489960SPRED2  rs6546146C > A0.3808.00e-07C1.11C
2p16.1chr2:60694033-61616575REL  rs34695944T > C0.3702.60e-08C1.13C
2q11.2chr2:99918896-100308644AFF3  rs10209110T > C0.4901.10e-08C1.11C
2q32.3chr2:190986040-191143008STAT4  rs13426947G > A0.1907.20e-10C1.15C
2q33.2chr2:203581104-203854006CD28  rs1980422T > C0.2308.70e-06C1.12C
2q33.2chr2:203768433-203951852CTLA4  rs11571302T > G0.4804.50e-08C1.12C
3p14.3chr3:58099168-58497903DNASE1L3  rs35677470G > A0.0801.70e-07C1.19C
4p15.2chr4:26026565-26130530RBPJ  rs932036A > T0.3002.00e-10C1.14C
4q27chr4:122016043-122644147IL21  IL2  rs78560100G > C0.0705.80e-04C1.13C
5q11.2chr5:56122309-56161300ANKRD55  rs71624119G > A0.2505.60e-20C1.23C
5q21.1chr5:102699259-103413530GIN1  rs39984G > T0.3209.30e-08C1.14C
6q21chr6:105955854-106110292PRDM1  rs6911690A > G0.1201.20e-04C1.15C
6q23.3chr6:137568592-137806067TNFAIP3  rs6920220G > A0.2002.30e-13C1.20C
6q25.3chr6:158904430-159121739TAGAP  rs629326T > G0.4101.10e-06C1.11C
6q27chr6:166937475-167134466RP11-517H2.6  CCR6  rs59466457G > A0.4402.70e-10C1.15C
7q32.1chr7:128911686-129137466IRF5  rs3807306G > T0.4901.90e-07C1.12C
8p23.1chr8:11426026-11546584BLK  rs4840565G > C0.2703.90e-06C1.10C
9p13.3chr9:34648421-34975511CCL21  rs2812378A > G0.3407.20e-10C1.15C
9q33.2chr9:120584375-121370602TRAF1  rs10739580T > C0.3301.70e-06C1.12C
10p14chr10:8041925-8082612GATA3  rs2275806A > G0.4104.60e-08C1.11C
10p15.1chr10:6346109-6394072PRKCQ  rs947474A > G0.1702.50e-05C1.11C
10p15.1chr10:5988280-6132638IL2RA  rs10795791A > G0.4003.00e-06C1.09C
10q21.2chr10:61995336-62137693ARID5B  rs12764378G > A0.2304.50e-10C1.14C
11p12chr11:36429978-36736361TRAF6  rs570676C > T0.3802.10e-03C1.08C
11q12.2chr11:61067850-61377180CD5  rs595158A > C0.4903.40e-08C1.09C
11q23.3chr11:118523399-118920441DDX6  rs4938573T > C0.1805.30e-07C1.15C
12q13.3chr12:57478937-58092238KIF5A  rs10683701None > None0.3302.30e-05C1.11C
15q14chr15:38522176-38662903RASGRP1  rs8043085G > T0.2501.40e-10C1.17C
15q23chr15:69667254-69758634TLE3  rs8026898G > A0.2901.40e-10C1.17C
16q24.1chr16:85956974-85990498IRF8  rs13330176T > A0.2204.00e-08C1.15C
17q12chr17:39226421-40083963IKZF3  rs2872507G > A0.4702.80e-09C1.10C
19p13.2chr19:10280033-10517872TYK2  rs34536443G > C0.0402.30e-14C1.61C
20q13.12chr20:45906012-46157817CD40  rs6032662T > C0.2401.40e-09C1.16C
21q22.12chr21:34454062-34639390RCAN1  rs2834512G > A0.1202.10e-08C1.16C
21q22.12chr21:35316472-35449600RUNX1  rs9979383T > C0.3605.00e-10C1.11C
22q12.3chr22:37142288-37166071IL2RB  rs3218251T > A0.2501.90e-07C1.13C
MHCchr6:32392711-32706866rs660895A > G1.00e-300C3.03C
Xq28chrX:153853745-154120938IRAK1  rs13397G > A0.1201.20e-12C1.27C


GDXHsS00019 meets the following criteria:

Criteria Name
Disease Tags
Study for a Disease 


PMIDTitleFirst AuthorJournalDisease(s)Date