A large-scale association study of Sjögren's Syndrome using individuals recruited to the Sjögren's Genetics Network (SGENE). A discovery phase was undertaken consisting on 395 cases with Sjögren's Syndrome (SJO) and 1,975 controls, typed on the Illumina Omnil-Quad array. Imputation was performed using IMPUTE2 and the European Impute2 1000 Genomes Phase 1 April 2012 reference panel. Replication was carried out 1,549 cases and 4,817 controls, typed on either the Illumina Immunochip or a custom array designed to include variants not on the Immunochip.  After QC, 648,937 SNPs were tested for association.  Only SNPs present on both the Immunochip and Ominl-Quad arrays (20,055) were used for the meta-analysis.

In total, 4 regions, including the HLA region, were shown to be associated with Sjögren's Syndrome at a level of genome-wide significance (GWS) in the meta-analysis. A further 25 regions showed suggestive association with Sjögren's Syndrome (P<5x10-5).

Study Type
Whole Genome Association Study
Exclusion Criteria


  • Poorly-defined cluster plots
  • MAF ≤ 0.01
  • Call rate ≤ 95%
  • Deviation from HWE (P ≤ 0.001)
  • Differential missingness between cases and controls (P ≤ 0.001)


  • Call rate < 95%
  • Excessive heterozygosity (>5 sd from the mean)
  • Relatedness was determined using identity-by-descent (IBD > 0.4)
  • Males were required to be heterozygous at rs2557523 and chrX hetereozygosity ≤ 10%
  • Females were required to be homozygous at rs2557523 and chrX hetereozygosity  > 10%

Study Association

RegionLocationGene(s)MarkerAlleleMAFP ValueOdds Ratio
1p21.2chr1:100744097-101194566VCAM1  rs115742139A > G0.0404.29e-06C1.68 (1.35-2.09)C
1p31.3chr1:67297383-67475484IL12RB2  rs6672745C > T0.1102.50e-05C1.35 (1.18-1.56)C
1p36.13chr1:19648175-19717654TMCO4  rs6699160T > C0.1301.70e-05C1.33 (1.17-1.51)C
1q23.3chr1:161418623-161665335FCGR2A  rs10800309G > A0.3406.72e-05C1.18 (0.99-1.41)D
1q31.3chr1:197342098-197970193C1orf53  rs61829103A > G0.0701.24e-05C1.56 (1.28-1.96)C
2p22.3chr2:33441389-33481588RASGRP3  rs13425999C > T0.0803.44e-06C1.56 (1.3-1.89)C
2p23.3chr2:24149269-24464482ITSN2  rs1545257G > A0.4802.47e-06C1.35 (1.15-1.59)D
2q31.1chr2:176778636-177025385rs1554770A > G0.4508.43e-06C1.23 (1.12-1.35)C
2q31.3chr2:180942889-181404099UBE2E3  rs6734603C > T0.2304.93e-05C1.25 (1.12-1.39)C
2q32.3chr2:190986040-191143008STAT4  rs13426947G > A0.1909.45e-09C1.34 (1.11-1.62)D
3q25.33chr3:159907335-160086566IL12A  rs485497G > A0.4801.17e-10C1.32 (1.12-1.55)D
4p16.3chr4:775809-1030564DGKQ  rs4690326C > A0.4701.05e-05C1.18 (1.0-1.39)D
5q33.1chr5:151012930-151103534TNIP1  rs7732451A > G0.1205.32e-07C1.36 (1.09-1.71)D
5q33.3chr5:160397457-160540930PTTG1  rs2431697T > C0.4303.76e-06C1.18 (1.0-1.39)D
5q35.2chr5:173790939-174111528CPEB4  rs359457T > C0.4508.96e-07C1.27 (1.15-1.39)C
6q14.1chr6:78604225-79155850PHIP  rs10943608T > C0.3706.22e-06C1.30 (1.11-1.53)D
6q14.1chr6:78604225-79155850IRAK1BP1  rs1507153C > A0.3607.09e-07C1.33 (1.13-1.57)D
6q21chr6:106084881-106180757PRDM1  rs526531G > A0.3102.93e-06C1.25 (1.05-1.49)D
6q23.3chr6:137552553-137804198TNFAIP3  rs6933404T > C0.2106.53e-08C1.18 (0.97-1.43)D
7p21.1chr7:17705861-18053735SNX13  rs6973480A > G0.4603.73e-05C1.21 (1.11-1.33)C
7q21.12chr7:87012779-87507702TP53TG1  rs11762311G > A0.0501.71e-05C1.53 (1.26-1.85)C
7q32.1chr7:128911686-129138653IRF5  rs17339836C > T0.1202.43e-16C1.65 (1.32-2.06)D
7q32.1chr7:128911686-129137466IRF5  rs4728142G > A0.4409.75e-17C1.29 (1.09-1.52)D
8p23.1chr8:11423764-11516364BLK  rs6998387G > A0.3207.96e-08C1.34 (1.13-1.59)D
8q24.21chr8:128105690-128266327MIR1208  rs759651T > C0.2001.22e-05C1.28 (1.15-1.43)C
10p15.1chr10:5986528-6083387IL15RA  IL2RA  rs1323651C > A0.3604.44e-05C1.22 (1.11-1.34)C
10q26.2chr10:127450875-127523711DOCK1  NPS  rs10830107A > G0.1704.70e-05C1.28 (1.14-1.44)C
11q23.3chr11:118523399-118920441CXCR5  rs4936443T > C0.2006.82e-08C1.27 (1.02-1.59)D
16q24.1chr16:85955578-85990498IRF8  rs11117431A > G0.2201.86e-05C1.3 (1.15-1.45)C
16q24.3chr16:89965824-90097180PRDM7  rs4785621G > A0.1201.45e-05C1.41 (1.2-1.64)C
MHCchr6:32350867-32661068HLA-DRA  rs3135394A > G0.2705.22e-113C3.52 (2.83-4.38)D
MHCchr6:32463352-32717903HLA-DQB1  rs3129716T > C0.2904.59e-112C3.29 (2.66-4.09)D
MHCchr6:32411770-32714430HLA-DQA1  HLA-DQA2  rs9271588C > T0.2701.37e-85C2.86 (2.38-3.45)D


GDXHsS00033 meets the following criteria:

Criteria Name
Disease Tags
Study for a Disease 


PMIDTitleFirst AuthorJournalDisease(s)Date