Table 2.
Risk loci associated with PBC identified by high-throughput genetic studies.
| Locus | GWAS of PBC |
Canadian/Italian/US iCHIP [51] |
UK iCHIP [52] |
Candidate gene(s) | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Study | SNV/RA | OR | p-value | Peak SNV/RA | OR | p-value | SNV/RA | OR | p-value | ||
| 1p36 | [50] | rs3748816/C | 1.33 | 3.15E-08 | rs10910108/G | 1.15 | 1.81E-03 | rs10797431/A | 1.15 | 1.44E-05 | MMEL1 |
| 1p31 | [45] | rs3790567/A | 1.51 | 2.76E-11 | rs72678531/C | 1.68 | 2.66E-23 | rs72678531/G | 1.61 | 2.47E-38 | IL12RB2 |
| 1q31 | [47] | rs12134279/T | 1.34 | 2.06E-14 | rs1539414/A | 1.26 | 3.46E-06 | rs2488393/A | 1.28 | 4.29E-12 | DENND1B |
| 2q12 | [49] | rs12712133/A | 1.14 | 5.19E-9 | IL1R1, IL1RL2 | ||||||
| 2q32 | [47] | rs10931468/A | 1.5 | 2.35E-19 | rs3024921/A | 1.75 | 4.45E-11 | rs3024921/A | 1.62 | 2.59E-18 | STAT4, STAT1 |
| 2q36 | [49] | rs4973341/C | 0.82 | 2.34E-10 | CCL20 | ||||||
| 3p24 | [47] | rs1372072/A | 1.2 | 2.28E-08 | rs1025818/G | 1.2 | 3.53E-05 | rs1025818/G | 1.13 | 1.89E-04 | PLCL2 |
| 3q13 | [47] | rs2293370/G | 1.35 | 2.53E-11 | rs1131265/G | 1.42 | 4.49E-09 | rs2293370/G | 1.39 | 6.84E-16 | CD80 |
| 3q25 | [45] | rs6441286/G | 1.54 | 2.42E-14 | rs9877910/T | 1.47 | 1.02E-17 | rs2366643/A | 1.35 | 3.92E-22 | IL12A |
| 4p16 | [49] | rs11724804/A | 1.22 | 9.01E-12 | DGKQ | ||||||
| 4q24 | [47] | rs7665090/G | 1.26 | 4.06E-12 | rs7665090/G | 1.18 | 1.00E-04 | rs7665090/C | 1.26 | 8.48E-14 | NFKB1 |
| 5p13 | [47] | rs860413/A | 1.3 | 1.02E-11 | rs700172/A | 1.27 | 1.63E-06 | rs6871748/A | 1.3 | 2.26E-13 | IL7R |
| 5q21 | [49] | rs526231 | 0.87 | 1.14E-08 | C5orf30 | ||||||
| 5q33 | [49] | rs2546890 | 0.87 | 1.06E-10 | IL12B | ||||||
| 6p21 | [45] | rs2856683/C | 1.75 | 1.78E-19 | rs7775055/C | 3.71 | 1.11E-33 | rs7774434/C | 1.57 | 1.30E-48 | HLA region |
| 6q23.3 | [49] | rs6933404 | 1.18 | 1.27E-10 | TNFAIP3, OLIG3 | ||||||
| 7p14 | [47] | rs6974491/A | 1.25 | 4.44E-08 | rs17259795/T | 1.24 | 1.19E-05 | rs73112661/G | 1.22 | 1.69E-07 | ELMO1 |
| 7q32 | [50] | rs10488631/C | 1.57 | 8.66E-13 | rs10488631/C | 1.56 | 2.52E-12 | rs35188261/A | 1.52 | 6.52E-22 | IRF5 |
| 9p32 | [48] | rs4979462/T | 1.57 | 1.85E-14 | |||||||
| 11q13 | [47] | rs538147/G | 1.23 | 2.06E-10 | rs694739/A | 1.18 | 2.85E-04 | rs694739/A | 1.18 | 1.96E-07 | RPS6KA4 |
| 11q23 | [47] | rs6421571/C | 1.37 | 2.69E-12 | rs7117261/C | 1.46 | 3.18E-10 | rs80065107/A | 1.39 | 7.20E-16 | CXCR5, DDX6 |
| 11q23 | [48] | rs4938534/A | 1.38 | 3.27E-08 | POU2AF1 | ||||||
| 12p13 | [47] | rs1800693/G | 1.22 | 1.80E-09 | rs1860545/T | 1.2 | 5.27E-05 | rs1800693/G | 1.27 | 1.18E-14 | TNFRSF1A,LTBR |
| 12q24 | rs11065979/A | 1.2 | 2.87E-09 | SH2B3 | |||||||
| 13q14 | rs3862738/G | 1.33 | 2.18E-08 | TNFSF11 | |||||||
| 14q24 | [47] | rs911263/T | 1.29 | 1.76E-11 | rs911263/A | 1.25 | 3.43E-06 | rs911263/T | 1.26 | 9.95E-11 | RAD51B |
| 14q32 | [47] | rs8017161/A | 1.22 | 2.61E-13 | TNFAIP2 | ||||||
| 16p13 | [47] | rs12924729/G | 1.29 | 2.95E-12 | rs413024/T | 1.31 | 2.29E-08 | rs12708715/G | 1.29 | 2.19E-13 | SOCS1, CLEC16A |
| 16q24 | [47] | rs11117432/G | 1.31 | 4.66E-11 | rs35703946/G | 1.27 | 6.10E-04 | rs11117433/G | 1.26 | 1.41E-09 | IRF8 |
| 17q12 | [50] | rs11557467/G | 0.72 | 3.50E-13 | rs907091/C | 1.29 | 3.43E-09 | rs17564829/G | 1.26 | 6.05E-14 | ORMDL3, IKZF3 |
| 17q21 | rs17564829/G | 1.25 | 2.15E-09 | MAPT | |||||||
| 19p12 | rs34536443/G | 1.91 | 1.23E-12 | TYK2 | |||||||
| 19q13 | [111] | rs3745516/A | 1.46 | 7.97E-11 | SPIB | ||||||
| 22q13 | [47] | rs968451/T | 1.27 | 1.08E-09 | rs715505/C | 1.41 | 9.58E-12 | rs2267407/A | 1.29 | 1.29E-13 | SYNGR1 |
Risk loci for PBC that have achieved genome-wide level of significance (p < 5 × 10−8) in at least one study. GWAS, genome-wide association study; iCHIP, Illumina immunoarray association study; OR, odds ratio; RA, risk allele; SNV, single nucleotide variant.
Adapted from Mells and Hirschfield [112].