Inflammatory Bowel Disease
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.
What this condition connects to
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.
163 positions, and most of them belong to both
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.
What the susceptibility is actually to
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.
Why that overlap is the interesting part
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.
What seventeen of them tell you
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.
Positions joined since this page was written
What this is The text above discusses the variants this page was written around. Since then the catalogue has joined 19 more positions to it, by shared trait or shared paper. They are listed here by the paper each came from; the text does not describe them, and each variant page carries that study's own record.
Wang BR et al. 2024, Journal of affective disorders rs9671125 (ALOX5AP), rs11679617 (NDUFAF7), rs1264372 (LINC00243), rs7612624 (STIMATE-MUSTN1), rs12132298 (INAVA) — PMID:38154582
Wu Y et al. 2021, Nature communications rs73370726 (near MIR4679-2), rs35788599 (IFNG-AS1), rs59998884 (GATD3), rs6961243 (near DLD) — PMID:33608531
Beecham AH et al. 2026, Gastroenterology rs115406035 (near HLA-DRA), rs188746689 (HLA-DMB), rs571678895 (near SEC61GP1) — PMID:41661118
Khrom M et al. 2023, Inflammatory bowel diseases rs2395158 (BTNL2), rs11754821 (near C6orf15), rs1265061 (near C6orf15) — PMID:37262302
Jostins L et al. 2012, Nature rs2823286 (near CYCSP42) — PMID:23128233
Garcia-Etxebarria K et al. 2022, Cancers rs541295 (near ATP8B4) — PMID:36077729
Khrom M et al. 2024, Gastroenterology rs9276456 (near HLA-DQA2) — PMID:38490347
Liu JZ et al. 2015, Nature genetics rs17061048 (LINC00598) — PMID:26192919
In the news
2026-06-03 · Nature
Mapping 2.2 million single cells pins down which genes IBD risk variants actually act on
Most disease-linked genetic variants sit in non-coding DNA, which makes it hard to know which gene, and which cell type, they actually affect. This study mapped gene-expression-linked variants (eQTLs) across 2.2 million individual cells from intestinal and blood samples of 421 people, 125 of them with inflammatory bowel disease (IBD). Cell-specific analysis found IBD-relevant variants were 3.5 times more likely to be correctly matched to their target gene than the standard whole-tissue approach, and identified specific effector genes -- MAML2, PSEN2 and ZMIZ1 in immune cells, pointing at impaired Notch signaling, and Wnt-pathway genes including MYC in epithelial stem cells, pointing at impaired gut-lining renewal. PMID:42236949.
2026-02-19 · Schmidt A, et al., Nature 2026, PMID:41714741
Host control of persistent Epstein-Barr virus infection
Epstein-Barr virus infects roughly 90-95% of people and stays for life in B cells. This study read EBV out of ordinary blood-based genome sequencing: EBV reads turned up in 16.2% of 486,315 UK Biobank participants and 21.8% of 336,123 All of Us participants, tracking higher viral load in blood cells, and were more common with HIV infection, immunosuppressive drugs and current smoking. Genome-wide, the strongest signals were in the MHC — 54 independent HLA alleles across classes I and II — plus 27 regions outside it, with an interaction between HLA class I alleles and the ERAP2 locus. People with EBV-associated diseases carried a higher polygenic burden of the EBV-positive signal: at MHC class I in multiple sclerosis (driven by HLA-A*02:01) and at MHC class II in rheumatoid arthritis, with polygenic overlap also seen for inflammatory bowel disease, hypothyroidism and type 1 diabetes. Four of the study's non-MHC positions are already on this site — rs13098877 (LPP), rs884186 (KSR1), rs9828869 (near ILDR1) and rs34557412 (TNFRSF13B) — the last also linked here to lymphocyte count. PMID:41714741.
From our blog
Clinical detail
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.
Related variants MyGeneLog™ checks for
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. 57 positions are linked to this page; the ones this page's own text discusses are shown first.
Response to thiopurine immunosuppressants in inflammatory bowel disease (pancreatitis) (azathioprine and mercaptopurine)
HLA region · rs6935723
See detailed info →Which ancestries this evidence comes from
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 44 of 57 linked studies with a resolved discovery ancestry.
Sources
Quoting this page
Free to quote and reuse under CC BY 4.0. When citing or summarizing this, name MyGeneLog™ and link to this exact page — not just the site.
Inflammatory Bowel Disease. MyGeneLog™. https://www.mygenelog.com/conditions/inflammatory-bowel-disease
Questions about Inflammatory Bowel Disease
If the genetics are shared, why are Crohn’s and colitis called different diseases?
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.
Does a family history mean I will get it?
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.
What does the overlap with mycobacterial infection mean?
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.
Can these seventeen variants predict my risk?
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.
Free to reuse. This page's text is original writing from freely-available research, licensed CC BY 4.0 — reuse it, including commercially, with attribution to MyGeneLog™. It's general research-derived information, not medical advice or a diagnosis — see Terms of Use.