The largest GWAS of primary sclerosing cholangitis to date found 4 new risk loci and showed the disease is genetically distinct from the inflammatory bowel disease it so often accompanies.
Primary sclerosing cholangitis (PSC) is a rare, progressive disorder in which the bile ducts become inflamed and scarred, eventually leading to bile duct destruction. About three-quarters of people with PSC also have inflammatory bowel disease (IBD), a co-occurrence close enough that the two conditions have long been studied together.
Ji et al. 2017 ran the largest GWAS of PSC to date: 4,796 cases and 19,955 population controls, finding 4 new genome-wide-significant loci. The most strongly associated variant, at one of those loci, affects splicing of UBASH3A.
The study also settled a genuinely open question: given how often PSC and IBD occur together, are they genetically the same disease wearing two names? The answer was no. Genetic correlation between PSC and ulcerative colitis (0.29) was significantly higher than between PSC and Crohn's disease (0.04) — but ulcerative colitis and Crohn's disease were themselves more genetically similar to each other (0.56) than either was to PSC. PSC shares real genetic ground with IBD, and more with one form of it than the other, but it is not simply IBD with a bile-duct complication; it has its own distinct genetic architecture.
This page's 7 variants — in or near IL2, BACH2, PRKD2, BCL2L11, FOXP1 (twice), and SGSM1 — come from this study. Worth being direct about: the UBASH3A splicing variant, the paper's single most emphasized finding, is not among this page's own variants.
PSC is diagnosed with imaging of the bile ducts (typically MRCP) and liver function tests, not with genotype. The variants here describe population-level genetic risk — they play no role in diagnosing an individual case or guiding treatment.
PSC monitoring and management — including screening for the liver and bile duct complications it can lead to — are guided by clinical and imaging findings, not by any variant on this page.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Primary Sclerosing Cholangitis comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 7 of 7 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
PSC is a rare, progressive disorder in which the bile ducts become inflamed and scarred, eventually leading to bile duct destruction. About three-quarters of people with PSC also have inflammatory bowel disease.
In 4,796 cases and 19,955 controls, it found 4 new genetic risk loci and showed that PSC, while sharing genetic ground with inflammatory bowel disease, is genetically its own distinct condition rather than a variant of IBD.
No. PSC is diagnosed with bile duct imaging and liver function tests, not genotype. This page describes population-level genetic risk factors.
No. The 2017 study found PSC is genetically correlated with ulcerative colitis more than with Crohn's disease, but has its own distinct genetic architecture separate from both.
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