Overview

Genome-wide association study of European subjects (2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (3,716 cases and 4,261 controls). Genotyping was performed on Illumina 1M-Duo, Hap370, 550K or 610-Quad platforms.  Imputation was carried out using the MaCH software package with HapMap3 CEU+TSI samples as reference sets.  A total of 1,143,634 genotyped or imputed SNPs were available for analysis. In total, 120 SNPs in 50 distinct loci were selected for follow-up, identifying a total of 28 risk loci reaching genome-wide significance, of which 6 are novel. The signal detected on chromosome 13 is likely a spurious signal from a single imputed SNP.

Study Type
Whole Genome Association Study
Samples
GroupPhenotypePopulationCasesControlsFamiliesTrios
DiscoveryPBCNULL276410475--
ReplicationPBCNULL37164261--
Exclusion Criteria

SNPs were excluded as below:-

  • Call rate < 95%
  • Minor allele frequency < 5%
  • Hardy-Weinbery equilibrium (HWE) P<10-5

Samples were excluded as below:-

  • High rates of missing data (> 90%)
  • Estimated proportion of identity by decent with another sample > 0.1
  • Gender discrepancies (X chromosome heterozygosity >0.2 for men and < 0.2 for women)

Study Association

RegionLocationGene(s)MarkerAlleleMAFP ValueOdds Ratio
1p31.3chr1:67297383-67475484IL12RB2  rs6679356T > C0.2107.49e-28D1.52D
1q31.3chr1:197342098-197969200DENND1B  rs17641524C > T0.1701.01e-11D1.30D
2p23.1chr2:30192259-30238062LBH  rs4952108C > T0.1905.05e-08D1.28D
2q12.1chr2:102130853-102478928IL1RL1  IL1RL2  rs12712133G > A5.19e-09C 
2q32.2chr2:190372346-190997672STAT4  STAT1  rs3771317T > C0.1402.32e-08D1.41D
2q36.3chr2:227747300-227809536CCL20  rs4973341T > C2.34e-10C 
3p24.3chr3:16822066-17110801PLCL2  rs1372072G > A0.3803.99e-08D1.20D
3q13.33chr3:119384793-119581808CD80  rs2293370G > A0.1404.26e-15D1.41D
3q25.33chr3:159973324-160104880rs485499T > C0.4001.43e-23D1.41D
4p16.3chr4:800141-1030564DGKQ  rs11724804G > A9.01e-12C 
4q24chr4:102467408-103205026NFKB1  rs1054037T > C0.4808.31e-10D1.22D
5p13.2chr5:35799194-36042117IL7R  rs860413A > C0.2104.73e-11D1.28D
5q21.1chr5:102777093-103428347PAM  C5orf30  rs526231C > T1.14e-08C 
5q23.1chr5:116028237-116304281rs2434360G > T1.04e-05C 
5q33.3chr5:159091760-159399302AC008697.1  rs2546890A > G1.06e-10C 
6q23.3chr6:137552553-137804198OLIG3  TNFAIP3  rs6933404T > C1.27e-10C 
7q32.1chr7:128911686-129137466rs10488631T > C0.0905.08e-23D1.59D
11q13.1chr11:64077211-64456055CCDC88B  rs510372C > T0.4301.68e-09D1.23D
11q23.3chr11:118523399-118920441DDX6  CXCR5  rs6421571C > T0.2001.78e-13D1.39D
12p13.31chr12:6312329-6354696TNFRSF1A  rs1800693C > T0.4901.87e-09D1.22D
12q24.12chr12:111287381-112592683SH2B3  rs11065978A > G0.3703.20e-08D1.19D
13q14.2chr13:50160568-50490165DLEU1  rs9591325T > C0.0601.07e-10D1.64D
14q24.1chr14:68071518-68485527RAD51B  rs911263T > C0.2702.28e-09D1.23D
14q32.32chr14:103013563-103150781TNFAIP2  rs2297067C > T0.1806.34e-19D1.39D
16p12.1chr16:27356013-27430771rs1859308C > T1.63e-07C 
16p13.13chr16:10923201-11218316SOCS1  DEXI  CLEC16A  rs12924729G > A0.3302.39e-14D1.32D
17q21.1chr17:39226421-40083963IKZF3  rs9303277T > C0.5002.57e-11D1.23D
19p13.2chr19:10285007-10517872TYK2  rs2304256C > A0.2901.05e-10D1.27D
19q13.33chr19:50324528-50530090SPIB  rs3745516G > A0.2401.22e-20D1.39D
22q13.1chr22:39259042-39372075SYNGR1  rs2069235G > A0.3202.23e-11D1.27D
MHCchr6:32463352-32717903rs7774434T > C0.4702.37e-56D1.68D

Criteria

GDXHsS00048 meets the following criteria:

Criteria Name
Details
Disease Tags
Study for a Disease 

Publications

PMIDTitleFirst AuthorJournalDisease(s)Date