Table 1 PBC risk loci identified in the current study.

From: International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

a. Confirmed risk loci (validation P <4.4 × 10−4 resulting in combined P <5 × 10−8)

Locus

SNP

Position (build 38)

A1/A2

Discovery

P

Validation

P

Joint

P

OR (95% CI)

Region (build 38)

Nearby genes and functional annotation*

Autoimmune overlap

2q12.1

rs12712133

102,249,813

A/G

1.62 × 10−5

7.94 × 10−5

5.19 × 10−9

1.14 (1.07–1.21)

102,118,975–102,438,307

IL1R1, IL1RL2†, FAM183DP, IL1RL1‡, IL18R1, LOC100422339, IL18RAP, MIR4772

CD, CeD

2q36.3

rs4973341

227,795,646

C/T

6.48 × 10−7

7.73 × 10−5

2.34 × 10−10

0.82 (0.74–0.90)

227,747,828–227,815,647

RNA5SP121, SNRPGP8, LOC100533842, CCL20†,§

 

4p16.3

rs11724804

971,991

A/G

3.67 × 10−7

4.25 × 10−6

9.01 × 10−12

1.22 (1.12–1.33)

853,681–1,014,424

GAK, TMEM175, DGKQ†, SLC26A1a, IDUA, FGFRL1

 

5q21.1

rs526231

103,345,680

T/C

3.10 × 10−5

9.39 × 10−5

1.14 × 10−8

0.87 (0.81–0.93)

102,939,698–103,416,571

PAM§, EIF3KP1, GIN1, PPIP5K2, C5orf30‡,§

RA

5q33.3

rs2546890

159,332,892

G/A

1.20 × 10−6

1.89 × 10−5

1.06 × 10−10

0.87 (0.82–0.93)

159,117,927–159,414,310

RNF145, UBLCP1, RNU4ATAC2P, IL12B, LOC285626†

Pso, MS, CD

6q23.3

rs6933404

137,638,098

C/T

9.47 × 10−7

2.84 × 10−5

1.27 × 10−10

1.18 (1.09–1.27)

137,571,557–137,803,754

LOC102723649, LOC442263, OLIG3†, TNFAIP3†

RA, SLE, SjS, CeD, UC, MS

b. Suggestive risk loci (validation P <1 × 10−3)

Locus

SNP

Position (build 38)

A1/A2

Discovery

P

Validation

P

Joint

P

OR for A1 (95% CI)

Region (build 38)

Nearby genes and functional annotation*

Autoimmune overlap

5q23.1

rs2434360

116,057,393

T/G

3.20 × 10−3

9.94 × 10−4

1.04 × 10−5

1.14 (1.05–1.23)

116,032,882–116,163,459

RPS25P6, ARL14EPL, COMMD10

 

16p11

rs1859308

27,386,677

T/C

7.72 × 10−5

5.37 × 10−4

1.63 × 10−7

0.85 (0.77–0.93)

27,359,133–27,434,733

IL4R, IL21R

 
  1. A1, tested allele; CD, Crohn disease; CeD, coeliac disease; CI, confidence interval; MS, multiple sclerosis; OR, odds ratio in validation cohorts; Pso, psoriasis; RA, rheumatoid arthritis; SjS, Sjogren syndrome; SLE, systemic lupus erythematosus; SNP, single-nucleotide polymorphism; UC, ulcerative colitis.
  2. PBC risk loci identified in the current study. SNPs were taken forward for validation based on having a discovery P value <2 × 10−5 (or, in the case of rs526231 and rs2434360, based on acting as a proxy for a SNP with a P value <2 × 10−5). Discovery P values were calculated using logistic regression of individual discovery data sets in ProbABEL followed by genomic control correction of individual discovery data sets in R and fixed-effects meta-analysis in META; validation P values were calculated using logistic regression of individual data sets in PLINK followed by fixed-effect meta-analysis in META; joint P values were calculated using fixed-effect meta-analysis of discovery and validation data sets in META; see Methods. Autoimmune overlap refers to overlap between risk loci for PBC and those of other autoimmune conditions.
  3. *Functional annotation.
  4. †Regulatory variants: The index SNP or variants in strong linkage disequilibrium (LD, r2≥0.8) with the index SNP at this locus overlap regulatory elements that are related to the annotated gene (Supplementary Table 3).
  5. ‡mQTLs: The index SNP or variants in strong LD are correlated to methylation related to the annotated gene (Supplementary Data 4).
  6. §eQTLs: The index SNP or variants in strong LD are correlated to expression of the annotated gene (see Supplementary Data 3).
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