A long-term inflammatory bowel disease in which the lining of the colon and rectum becomes inflamed and ulcerated, causing bloody diarrhoea, urgency and abdominal cramping that flare and remit over years.
Ulcerative colitis (UC) is a chronic disease in which the inner lining of the large intestine — the colon and rectum — becomes inflamed and develops small open sores called ulcers. It is one of the two main forms of inflammatory bowel disease (IBD); the other is Crohn's disease. The two are related but not identical: ulcerative colitis affects only the colon and rectum and involves only the innermost layer of the bowel wall, whereas Crohn's disease can appear anywhere from mouth to anus and can burrow through the full thickness of the wall.
The most common symptoms are diarrhoea that often contains blood or mucus, a sudden and hard-to-ignore urge to empty the bowels, cramping pain (often on the lower left side), and passing frequent small stools including at night. Because the inflammation is ongoing and the bowel bleeds, many people also become tired and anaemic, lose weight, or run a low fever. Symptoms range widely: some people have mild disease confined to the last few inches of the rectum and manage well for decades, while others have inflammation across the whole colon and need hospital care.
Ulcerative colitis is a relapsing and remitting condition. Periods of active inflammation, called flares, alternate with periods of remission in which a person may feel completely well. This pattern is one of the defining features of the disease, and much of modern treatment is aimed at getting a person into remission and keeping them there rather than at curing the disease outright.
The condition can start at any age but is most often diagnosed between the late teens and the mid-thirties, with a second, smaller peak in people in their fifties and sixties. Unlike many autoimmune conditions, it affects men and women in broadly similar numbers. It is most common in Europe and North America, though its incidence has been rising in newly industrialised regions of Asia, South America and Africa — a pattern that points strongly to environmental and lifestyle factors acting alongside genetics.
Nobody develops ulcerative colitis from a single cause. The current understanding is that it arises when several things line up: an inherited tendency toward a particular kind of immune response, a gut microbiome that is out of balance, a weakened intestinal barrier that lets bacteria come into closer contact with immune cells than they should, and environmental triggers. Because dozens or hundreds of genetic variants each contribute a little, having a relative with IBD raises your risk but is nowhere near a guarantee — the large majority of people with ulcerative colitis have no affected close relative at all.
Diagnosis is not made from a genetic test or a blood test alone. A doctor who suspects ulcerative colitis will typically check stool samples to rule out infections that mimic it, measure inflammation markers in blood and stool, and then perform a colonoscopy — passing a camera through the colon — while taking small tissue samples. It is the appearance of the bowel lining plus what the pathologist sees under the microscope that confirms the diagnosis and distinguishes ulcerative colitis from Crohn's disease and from infectious causes of colitis.
Ulcerative colitis is not confined to the gut. A minority of people also develop inflammation in the joints, eyes, skin or bile ducts. And because long-standing inflammation of the colon raises the risk of colorectal cancer over time, people with extensive, long-duration disease are enrolled in regular surveillance colonoscopy programmes. Both of these are reasons the condition is managed as a lifelong relationship with a gastroenterology team rather than as a one-off illness.
A note on what genetics can and cannot tell you here. The specific DNA variants studied in relation to ulcerative colitis — including the two linked on this page — are common variants. They are carried by a large share of healthy people and each shifts risk only slightly. They are research findings from population studies, not diagnostic tests, and no combination of them can tell an individual whether they have or will develop the disease.
Ulcerative colitis is a mucosal, continuous colitis beginning at the rectum and extending proximally to a variable degree. Diagnosis is clinicopathological: there is no single confirmatory test. It rests on compatible symptoms of at least several weeks' duration, exclusion of enteric infection (including Clostridioides difficile and, where relevant, CMV), and endoscopic plus histological confirmation. Ileocolonoscopy with segmental biopsies is the reference standard; characteristic histology includes crypt architectural distortion, basal plasmacytosis, crypt abscesses and a mucosa-limited chronic inflammatory infiltrate. Faecal calprotectin is a useful non-invasive marker of mucosal inflammation for triage and for monitoring, but is not disease-specific.
Disease extent is described by the Montreal classification: E1 ulcerative proctitis (limited to the rectum), E2 left-sided or distal colitis (extending to but not beyond the splenic flexure), and E3 extensive colitis or pancolitis (proximal to the splenic flexure). Extent matters because it drives the choice between topical and systemic therapy and determines colorectal cancer surveillance intervals. Severity of a flare is graded separately, historically by the Truelove and Witts criteria and in trials by composite indices such as the Mayo score.
Key differential diagnoses include Crohn's colitis, infectious colitis, drug-induced (notably NSAID) colitis, ischaemic colitis, diverticular segmental colitis and, in immunocompromised patients, opportunistic infection. Recognised extraintestinal manifestations include peripheral and axial arthropathy, episcleritis and uveitis, erythema nodosum, pyoderma gangrenosum and primary sclerosing cholangitis, the last of which independently escalates colorectal cancer risk and surveillance intensity.
IBD is a polygenic, immune-mediated disorder. Large-scale association work has accumulated well over 200 independent risk loci for IBD; de Lange and colleagues (2017) added 25 loci to a prior tally of 215, and Anderson and colleagues (2011) had earlier raised the count of confirmed ulcerative colitis loci specifically to 47. Most loci are shared between ulcerative colitis and Crohn's disease, and implicated pathways cluster around innate bacterial handling, epithelial barrier integrity, IL-23/Th17 signalling and integrin-mediated leukocyte trafficking. Collectively these common variants still explain only a modest fraction of disease heritability.
Distinct from this polygenic picture, a small number of very-early-onset IBD cases — typically presenting under age 6 — are caused by rare, high-penetrance monogenic defects (for example in IL10, IL10RA, IL10RB, XIAP, NCF2 or NCF4). Those are genuinely Mendelian conditions and are diagnosed by sequencing, not by the common-variant genotyping described below. The variants on this page belong to the polygenic category and should not be conflated with monogenic IBD.
rs5771069 (IL17REL, 22q13.33). Franke and colleagues (2010, Nature Genetics) performed a genome-wide association analysis of roughly 1.9 million SNPs in 1,043 German ulcerative colitis cases and 1,703 controls, then followed the top signals into six European replication panels totalling 2,539 cases and 5,428 controls. The 22q13 signal at IL17REL reached an overall study-sample p-value of 4.21 × 10-8. The GWAS Catalog records the risk allele as G with a frequency near 0.49 and an odds ratio of about 1.17 (95% CI 1.11–1.25) — that is, roughly a 17% relative increase in odds per risk allele in a population where the allele is close to a coin flip. In the subsequent Anderson (2011) ulcerative colitis meta-analysis the same SNP gave a smaller effect, OR ≈ 1.11 (95% CI 1.07–1.16, p = 2 × 10-7), and the locus was again associated with ulcerative colitis in the de Lange (2017) IBD GWAS (p = 2 × 10-10). Independent replication across European populations has not been uniform: a Baltic, Danish and Norwegian replication case-control study (BMC Medical Genetics 2011, PMID 21995314) found the association reached significance only in the Norwegian panel and not in the Danish one, which is a reminder that effects this small are sensitive to sampling and population structure. IL17REL encodes an interleukin-17 receptor E-like protein; the causal gene at the locus has not been definitively assigned, and PIM3 and TTLL8 also sit within the associated interval. Notably the same SNP has since been reported at genome-wide significance for type 2 diabetes in a multi-ancestry meta-analysis, which is a typical illustration of pleiotropy at common-variant loci rather than evidence of a shared mechanism.
rs2315008 (TNFRSF6B, 20q13.33). This variant was identified by Kugathasan and colleagues (2008, Nature Genetics) in a genome-wide analysis stratified by age of onset: 1,011 individuals of European ancestry with paediatric-onset IBD and 4,250 matched controls, with replication in independent cohorts. The paper reported the association in the protective direction, rs2315008[T] with OR = 0.74 and p = 6.30 × 10-8; expressed per copy of the more common G allele (frequency ≈ 0.69) this corresponds to an odds ratio of roughly 1.36, which is how the GWAS Catalog records it. Two points deserve emphasis. First, the discovery cohort was paediatric-onset IBD encompassing both Crohn's disease and ulcerative colitis, so this is an IBD-wide rather than a UC-specific signal, and the strongest downstream evidence at this locus has been for Crohn's disease. Second, the association is with the 20q13.33 region, which contains TNFRSF6B, ZGPAT, ARFRP1 and other genes; the causal gene has not been formally established. TNFRSF6B encodes decoy receptor 3 (DcR3), a soluble receptor that binds and neutralises TNF-superfamily ligands including FasL, LIGHT and TL1A (TNFSF15) — a biologically attractive candidate given that TNFSF15 is itself an established IBD locus and an active therapeutic target. Supporting a genuine inflammatory role for this region, rs2315008 has independently been associated at genome-wide significance with neutrophil count (Chen et al. 2020, per-allele beta ≈ 0.016) and with circulating C-reactive protein (Ligthart et al. 2018) in very large biobank analyses.
Both variants are common polymorphisms with small per-allele effects identified in populations of European ancestry. Neither is causal in the Mendelian sense, neither is diagnostic, and neither is used in routine clinical practice for prediction, diagnosis or treatment selection. Effect sizes of this magnitude (OR 1.1–1.4) shift an individual's absolute lifetime risk only marginally from a baseline that is itself well under 1%, and the reported estimates may not transfer to non-European populations, in whom these loci are far less well characterised. Genotype at either SNP should not influence clinical decision-making.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Ulcerative Colitis comes down to these specific, well-studied positions — not a diagnosis.
No. Both are common variants — the rs5771069 risk allele is found on about half of chromosomes in people of European ancestry (an allele frequency near 0.49, meaning roughly three quarters of people carry at least one copy), and the rs2315008 risk allele on about two thirds of chromosomes (frequency near 0.69, so roughly nine in ten people carry a copy). Each shifts the odds only slightly (roughly 11-36% in relative terms per copy) against a baseline lifetime risk well under 1%. The overwhelming majority of carriers never develop the disease, and many people who do have it carry neither risk allele.
Not in a simple way. It does not follow a dominant or recessive pattern from a single gene. Instead, more than 200 common variants each contribute a small amount of risk, together with gut bacteria, the intestinal barrier and environmental factors. Having a parent or sibling with IBD raises your risk, but most people diagnosed have no affected close relative. A rare exception is very-early-onset IBD appearing in infancy, which can sometimes be caused by a single high-impact gene defect and is investigated by sequencing.
By clinical assessment plus colonoscopy with biopsies, after infections have been ruled out with stool testing. The endoscopic appearance of continuous inflammation starting at the rectum, combined with the microscopic findings from the tissue samples, is what confirms the diagnosis and separates it from Crohn’s disease and from infectious colitis. Blood tests and faecal calprotectin support the picture but cannot make the diagnosis on their own, and no genetic test is used to diagnose it.
Ulcerative colitis is confined to the colon and rectum, involves only the innermost lining of the bowel, and spreads continuously upward from the rectum. Crohn’s disease can affect any part of the digestive tract, can involve the full thickness of the bowel wall, and typically appears in patches with normal bowel in between. They share many genetic risk loci, which is why both fall under the umbrella term inflammatory bowel disease.
Because they were found by genome-wide association studies, which are designed to detect common variants present in a large share of the population. A variant that common cannot have a large effect or it would be far rarer, since natural selection would act against it. Variants like these are valuable for pointing researchers toward biological pathways — the TNFRSF6B region, for instance, implicates TNF-superfamily signalling — but they are not useful for predicting any individual person’s outcome.
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