Overview

High-density genotyping study involving 5,850 individuals with systemic sclerosis (SSc) and 9,401 unrelated, healthy controls of European ancestry using the Illumina ImmunoChip platform. A total of 126,270 SNPs were available for analysis after the QC process. For relatedness analysis, PLINK (v1.07) was used to calculate identity-by-descent. Association analysis and population stratification control was perfomed using linear mixed models as implemented in FaST-LMM(v1.05). Imputation was implemented in IMPUTE2 with the use of the 1000 Genomes Phase 3 reference panel. Association at genome-wide significance (P < 5x10-8) was observed for 3 novel loci, as well as validating previously reported SSc risk loci (including the HLA region). 

Study Type
Case-Control Study
Samples
GroupPhenotypePopulationCasesControlsFamiliesTrios
DiscoverySSC18333466--
ReplicationSSC40175935--
Exclusion Criteria
Samples were excluded due to:-
  • Inferred ethnicity by principal-component analysis
  • Duplication
Markers were excluded due to:-
  • Call rate ≤ 95%
  • Deviation from Hardy-Weinberg equilibrium in controls (P < 1x10-5)

Study Association

RegionLocationGene(s)MarkerAlleleMAFP ValueOdds Ratio
1p13.2chr1:113302837-114011552PTPN22  rs76853721G > A7.10e-03D1.61D
1p31.3chr1:67297383-67475484IL12RB2  rs6672745C > T3.72e-05D1.45D
1p34.3chr1:35169091-36096252KIAA0319L  rs1203138G > A2.60e-01D1.15D
1p36.23chr1:7851039-8140268TNFRSF9  rs9657998A > G5.30e-03C1.76D
1q25.1chr1:173128850-173331701TNFSF4  rs35086785T > G3.81e-05D1.27D
2q32.3chr2:190984302-191133220STAT4  rs11893432C > G2.94e-12D1.44D
3p14.3chr3:58171419-58563570PXK  rs4681851C > G4.00e-08D1.58D
3p14.3chr3:58099168-58497903DNASE1L3  rs35677470G > A0.0623.36e-16C1.70D
3q25.33chr3:159883974-160033824SCHIP1  IQCJ-SCHIP1  IL12A  rs77583790G > A0.0051.22e-11C2.45D
4p15.2chr4:21998947-22320161KCNIP4  ADGRA3  rs4235295A > G5.30e-03C1.25D
4q24chr4:101788151-102199886BANK1  rs115154558A > G2.47e-03D2.23D
4q24chr4:102467408-103091883NFKB1  rs1598859T > C1.11e-04D1.19D
5q33.1chr5:151011910-151094519TNIP1  rs184010692G > A2.33e-03D2.65D
6q21chr6:106150148-106380042ATG5  rs9373839T > C0.1853.75e-08C1.24D
6q23.3chr6:137818557-137981174TNFAIP3  rs113661016C > T8.78e-04D2.37D
7p12.1chr7:50831471-51013280GRB10  rs11238357T > C5.28e-04D1.40D
7q21.2chr7:93054241-93390636SAMD9L  rs7810211T > C6.68e-02D1.23D
7q32.1chr7:128911686-129138653IRF5  rs62478615G > C1.01e-10D1.53D
8p22chr8:19101856-19177115PSD3  rs11204021C > T8.78e-03D1.16D
8p23.1chr8:11427516-11546584BLK  rs2736345A > G2.60e-05D1.32D
10p15.1chr10:5988280-6129441IL2RA  rs2245675G > A9.46e-04D1.25D
11p15.5chr11:413012-721570IRF7  rs1131665T > C5.67e-03D1.15D
11q23.3chr11:118465212-118911765DDX6  TREH  rs7130875T > C1.29e-07C1.18D
12p12.1chr12:24245118-24304282SOX5  rs12371851C > T8.89e-03D1.19D
12q13.2chr12:55958153-56404651ESYT1  RPL41  rs77568502C > G8.59e-04D2.34D
16p11.2chr16:30892358-31375541ITGAM  rs11574632C > T4.73e-05D1.27D
16q24.1chr16:86403083-86442831IRF8  rs16941172T > C3.32e-03D1.46D
17q21.1chr17:39231017-40098436GSDMA  rs3902025T > G2.81e-05C1.14D
18q22.2chr18:69841693-69903977CD226  rs75302561G > A1.31e-02D1.47D
MHCchr6:31289383-31419380HLA-B  rs2442719A > G0.4109.55e-23D1.51 (1.39-1.64)D

Criteria

GDXHsS00034 meets the following criteria:

Criteria Name
Details
Disease Tags
Study for a Disease 

Publications

PMIDTitleFirst AuthorJournalDisease(s)Date