An autoimmune disease that slowly destroys the small bile ducts inside the liver, overwhelmingly in women. Fifteen risk variants across five studies on three continents converge on the immune system, not the liver itself.
Solid lines are connections this site curates. Dashed lines mean the two ends share a research paper — worth knowing, and not a claim that one explains the other.
Primary biliary cholangitis (PBC) is an autoimmune disease in which the immune system slowly destroys the small bile ducts inside the liver, leading over years to cholestasis (impaired bile flow) and, in advanced cases, cirrhosis. Worldwide prevalence estimates range widely, from about 1.91 to 40.2 per 100,000 people, and appear to be rising over time; a recent national study in Colombia found a prevalence of 14.7 per 100,000, with marked female predominance and disease most common between ages 50 and 69.
The disease used to be called "primary biliary cirrhosis." In 2015, a group of hepatology researchers and societies renamed it "primary biliary cholangitis," published simultaneously across five journals — because many people with the disease never develop cirrhosis at all, and the old name overstated how advanced the disease necessarily is.
Genome-wide association studies in the UK, Japan, Italy/Canada, an international European meta-analysis, and China have together found dozens of PBC risk loci. Fifteen of them are the variants on this page:
Liu et al. 2010 combined an Italian discovery cohort with a Canadian dataset and found new loci at SPIB (rs3745516, OR=1.46) and elsewhere, replicating IL12A (rs6441286). Mells et al. 2011, the UK PBC Consortium (1,840 cases, 5,163 controls discovery; 620 cases, 2,514 controls replication), found 12 new loci and replicated every previously known one — ten of this page's variants come from here, including IL12RB2, CD80, TNFRSF1A, CLEC16A, IRF8, DENND1B, TNFAIP2 and the MHC region itself. Nakamura et al. 2012 ran the same search in a Japanese population and found POU2AF1 (rs4938534) and IL7R. Cordell et al. 2015's international meta-analysis (2,764 cases + 10,475 controls, validated in 3,716 more cases) found six further loci, including PAM, and used pathway analysis to point specifically at JAK-STAT and IL12/IL27 signalling — immune pathways that existing drugs already target. Qiu et al. 2017's study in a Han Chinese population found HLA-DPB1 (rs9501251) among 14 loci.
Read together, these genes tell a coherent story rather than a scattered list: HLA and CD80 sit in antigen presentation and T-cell activation, IL12A/IL12RB2 sit in the same interleukin-12 signalling pathway on both sides of it, and SPIB/POU2AF1 both help direct B-cell and antibody-producing plasma-cell development — consistent with PBC's hallmark feature, antimitochondrial antibodies present in the large majority of patients.
Liu et al. 2012 used dense fine-mapping (Immunochip) across 2,861 people with PBC and 8,514 controls, all from the UK, and found 3 new genome-wide-significant loci — bringing the total known PBC susceptibility loci to 25 at the time. Two of the clearest are on this page: rs3024921, in STAT1 (odds ratio 1.62, p=2.59×10⁻¹⁸), and rs35188261, in IRF5 (odds ratio 1.52, p=6.52×10⁻²²).
Three more independent signals from the same study are on this page too: rs668998 (IL12A), rs11064157 (near TNFRSF1A, LTBR and SCNN1A) and rs12708715 (near SOCS1 and CLEC16A) — each confirmed at genome-wide significance, with odds ratios in a similar range to the two above.
One more variant is worth a specific mention: rs80073729, a rare variant (present in fewer than 1 in 200 people) that turned out to be the third independent PBC signal at the same 16p13 locus as rs12708715. The paper notes this exact SNP had, separately, recently been associated with celiac disease — one more example, alongside others already on this page, of autoimmune risk loci that are shared across conditions rather than specific to one.
2025-02-27 · Cross-Phenotype Genome-Wide Association Study on the Shared Genetic Susceptibility to Systemic Sclerosis and Primary Biliary Cholangitis. Arthritis & Rheumatology. 2025. DOI:10.1002/art.43081
Patients with systemic sclerosis (SSc) have an elevated risk of primary biliary cholangitis (PBC), and this study quantified how much of that reflects shared genetics. It found a remarkably strong global genetic correlation between the two conditions (rg=0.84, P=1.7x10^-6) -- a very high value, indicating substantial overlap in genetic risk architecture, not just occasional clinical co-occurrence. Cross-phenotype meta-analysis identified 44 non-HLA loci reaching genome-wide significance, with 9 showing evidence of a shared causal variant between the two diseases, 5 of them newly reported. Integrating fine-mapping, colocalization with gene-expression and protein-expression data, and phenome-wide association analysis, the study prioritized 5 novel candidate causal genes: CD40, ERAP1, PLD4, SPPL3 and CCDC113. The CD40 risk locus specifically colocalized with trans-protein quantitative trait loci for multiple plasma proteins involved in B-cell function -- a coherent mechanistic thread, since both SSc and PBC involve autoantibody production driven by B cells. This site's systemic sclerosis page carries 10 variants and primary biliary cholangitis page carries 23; none of these five genes are currently on either.
PBC is diagnosed with blood tests (liver enzymes, antimitochondrial antibodies) and sometimes liver biopsy or imaging, not by genotype. First-line treatment is ursodeoxycholic acid, which slows progression in most patients; obeticholic acid and other second-line therapies exist for people who respond inadequately. None of that is decided by the variants on this page.
The 2015 pathway analysis pointing to JAK-STAT and IL12/IL27 signalling is worth taking seriously precisely because those pathways already have real, approved drugs aimed at them for other autoimmune diseases — a genuine link from a statistical association to a plausible treatment target, not just a name on a list. That said, no JAK inhibitor or IL-12/23 blocker is a standard PBC treatment today; this is a research lead, not current practice.
None of the fifteen variants here changes how PBC is diagnosed or treated. Each is a common variant with a modest individual effect on risk, found in a population of thousands, not a predictive test for one person.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Primary Biliary Cholangitis comes down to these specific, well-studied positions — not a diagnosis. 26 positions are linked to this page; the ones this page's own text discusses are shown first.
near HLA-DQB1 · rs1794280
See detailed info →The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 23 of 26 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
No. PBC is diagnosed with blood tests, primarily antimitochondrial antibodies and liver enzymes, sometimes with imaging or biopsy. These variants come from genome-wide association studies and are not used diagnostically.
In 2015, hepatology researchers and societies renamed it "primary biliary cholangitis" — published simultaneously across five journals — because many people with the disease never develop cirrhosis, and the old name overstated how advanced it necessarily is.
One finding does: a 2015 pathway analysis pointed to JAK-STAT and IL12/IL27 signalling, pathways that already have approved drugs for other autoimmune diseases. That is a research lead worth taking seriously, not a current standard treatment for PBC.
It genuinely does — the disease shows marked female predominance in every population studied. The genetic loci found so far do not by themselves explain the size of that sex difference.
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