Overview

Fine mapping was performed on Immunochip platform, in 3789 cases with Primary sclerosing cholangitis (PSC) and 25079 controls of European ancestry across 130422 markers. PLINK (version 1.07) was used to calculate genotype call rate and heterozygosity call rate. Aberrant (clustering algorithm) was used to identify outlying samples. Principal-component analysis (PCA) was performed using SMARTPCA (Eigenstrat). Imputation was performed using IMPUTE2 with the 1000 Genomes Project Phase 1 reference panel. Association analysis was performed using a linear mixed model as implemented in MMM. This study reported 12 non-HLA genome-wide significant  (P < 5 x 10-8) loci, out of which 9 are novel.
 
Study Type
Case-Control Study
Samples
GroupPhenotypePopulationCasesControlsFamiliesTrios
DiscoveryPSC378925079--
Exclusion Criteria
Samples:
 
Initially SNPs with call rate < 80% were removed, followed by removing samples that have
  • Missingness/heterozygosity outliers
  • Ancestry outliers 
  • Duplicates (identity by descent ≥ 0.9)
SNP:
  • Deviation from Hardy-Weinberg equilibrium (P < 10-5)
  • Differential missingness between cases and controls (P < 10-5)
  • Call rate < 98%
  • Minor allele frequency < 0.1%
  • Poor signal intensity clusters
 

Study Association

RegionLocationGene(s)MarkerAlleleMAFP ValueOdds Ratio
1p36.32chr1:2431888-2879054MMEL1  TNFRSF14  rs3748816A > G0.3447.41e-12D1.2 (1.14-1.27)D
2q33.2chr2:203581104-203858418CD28  rs7426056G > A0.2291.89e-20D1.30 (1.23-1.37)D
3p21.31chr3:48465783-50711580MST1  rs3197999G > A0.2852.45e-26D1.33 (1.26-1.40)D
4q27chr4:122047009-122646623IL21  IL2  rs13140464C > A0.1648.87e-13D1.3 (1.27-1.41)D
6q15chr6:90298308-90382971BACH2  rs56258221A > G0.1838.36e-12D1.23 (1.16-1.31)D
10p15.1chr10:5988280-6132638IL2RA  rs4147359G > A0.3498.19e-17D1.24 (1.18-1.30)D
11q23.1chr11:111449004-112118869SIK2  rs7937682C > G0.2653.17e-09D1.17 (1.11-1.24)D
12q13.11chr12:47788458-47837647HDAC7  rs11168249A > G0.4665.49e-09D1.15 (1.10-1.21)D
12q24.12chr12:111278572-112592683SH2B3  ATXN2  rs3184504G > A0.4885.91e-11D1.18 (1.12-1.24)D
18q22.2chr18:69836289-69902924CD226  rs1788097G > A0.4833.06e-08D1.15 (1.10-1.21)D
19q13.32chr19:46648121-46811943STRN4  PRKD2  rs60652743A > G0.1646.51e-10D1.25 (1.16-1.33)D
21q22.2chr21:39081110-39111851PSMG1  rs2836883G > A0.2723.19e-17D1.28 (1.2-1.35)D

Criteria

GDXHsS00032 meets the following criteria:

Criteria Name
Details
Disease Tags
Study for a Disease 

Publications

PMIDTitleFirst AuthorJournalDisease(s)Date