Crohn’s disease and ulcerative colitis are diagnosed separately, treated differently and inherited almost identically. Of the 163 positions found for inflammatory bowel disease, most contribute to both.
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.
Inflammatory bowel disease is the name for two conditions: Crohn's disease, which can inflame any part of the gut from mouth to anus and does so in patches through the full thickness of the wall, and ulcerative colitis, which inflames the lining of the large bowel continuously from the rectum upwards.
A gastroenterologist tells them apart by where the inflammation is and how deep it goes. The genetics barely tells them apart at all.
A 2012 meta-analysis combined the genome-wide scans for both diseases across more than 75,000 cases and controls. It added 71 new associations, bringing the total to 163 loci for inflammatory bowel disease — and its central finding was about how those loci were distributed:
Most loci contribute to both phenotypes.
That is a strange sentence to read if you have been told you have one disease and not the other. Two clinical pictures, two treatment paths, largely one inherited susceptibility underneath.
The genes near these positions do not describe a bowel. They describe an immune system deciding what to tolerate.
rs1569723 sits at CD40, a switch on the surface of immune cells. rs630923 is at CXCR5, which directs lymphocytes to where they gather. rs2231884 is at RELA, a component of NF-κB — the master control for inflammatory genes. rs11168249 is near VDR, the receptor vitamin D acts through.
The 2012 analysis pushed this further than a gene list. It found the same loci implicated in ankylosing spondylitis and psoriasis — a spine and a skin — and, more surprisingly, considerable overlap with susceptibility to mycobacterial infection.
Variants that make a gut attack itself should be selected away. Many of these were not: the study found signatures of both directional selection, where one allele has been favoured over human history, and balancing selection, where populations have held on to both.
An immune system tuned to deal harshly with mycobacteria is an immune system that has been useful for a very long time. Inflammatory bowel disease looks, from the genetics, like part of the price of that setting — a defence calibrated for a world with more pathogens in it, firing in a world with fewer.
This is what the study meant by host–microbe interactions shaping the architecture of the disease. It is not a metaphor about gut bacteria on a supplement label; it is a claim about which alleles survived.
Nothing about you individually. Each of these positions shifts risk by a few percent against a lifetime risk that is well under one in a hundred, and 163 of them are known. Seventeen are on this page.
There is no genetic test for inflammatory bowel disease and no genotype that changes what a gastroenterologist does. Diagnosis is endoscopy, biopsy, imaging and blood and stool markers — not saliva.
What the genetics has changed is the treatment landscape rather than the diagnostic one: several of the pathways found this way are the pathways today's biologic drugs are aimed at. That is a slow benefit, and it is a real one.
Source. Jostins et al. (Nature 2012) meta-analysed Crohn's disease and ulcerative colitis genome-wide association scans with extensive validation of significant findings, a combined total of more than 75,000 cases and controls. 71 new associations were identified, giving 163 loci meeting genome-wide significance for inflammatory bowel disease. The authors report that most loci contribute to both phenotypes, that both directional and balancing selection effects are evident across them, that many are implicated in other immune-mediated disorders — most notably ankylosing spondylitis and psoriasis — and that there is considerable overlap between IBD susceptibility loci and loci for mycobacterial infection, a relationship emphasised by gene co-expression network analysis.
Relationship to the Crohn's and ulcerative colitis pages. This page is the shared axis, not a superset. Where a locus is disease-specific it belongs on the specific page; the seventeen positions listed here were recorded by the collector under the trait "Inflammatory bowel disease" rather than under either diagnosis, and are presented as such.
Genes at the listed positions. RELA (NF-κB p65 subunit), CD40, CXCR5, VDR, GPR183, CEBPB, FOS, LITAF, RPS6KB1, ADCY3, CRTC3, RABEP2, KIR2DL1, and positions near EMSY, TMEM135, ZBTB40 and CTH. Nearest-gene annotation is not a causal claim; for most common-variant associations the effector gene is not established.
Clinical use. None of these variants is used diagnostically or prognostically. Diagnosis rests on endoscopic and histological findings with supporting imaging and laboratory markers. Genotype does not currently direct choice of therapy in inflammatory bowel disease, with the separate exception of thiopurine metabolism — see the Crohn's disease and ulcerative colitis pages, where TPMT and NUDT15 notes are recorded against the drugs they apply to.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Inflammatory Bowel Disease comes down to these specific, well-studied positions — not a diagnosis.
Because they behave differently in a patient, which is what a diagnosis is for. Crohn’s can affect anywhere from mouth to anus, in patches, through the whole thickness of the bowel wall; ulcerative colitis affects the lining of the large bowel continuously from the rectum. Surgery, complications and monitoring differ accordingly. The shared inheritance is a statement about susceptibility, not about what happens next.
No. Risk is higher with an affected close relative and still low in absolute terms — inflammatory bowel disease affects well under one percent of people. There is no genetic test that resolves this, and no preventive treatment a positive result would unlock.
That some of the same alleles affecting how forcefully the immune system handles mycobacteria also affect susceptibility to inflammatory bowel disease. It is a finding about shared genetic architecture. It is not a claim that an infection causes the disease, and it is not a reason to seek any test or treatment.
No. Each shifts the odds by a small amount, 163 loci are known, and even all of them together do not produce a clinically useful individual prediction. This page exists to explain what was found, not to score anybody.
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