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Inflammatory bowel disease
Also known as IBD · Crohn's disease · Ulcerative colitis
Most people who develop Crohn's disease or ulcerative colitis do not carry a single faulty gene. Instead, their risk reflects many common DNA variants spread across the genome, each adding a small amount, together with environmental triggers such as smoking, diet and the gut microbiome. A polygenic risk score sums these many small genetic effects into one estimate of inherited susceptibility.
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Overview
Inflammatory bowel disease (IBD) is an umbrella term for long-term conditions in which the digestive tract becomes inflamed, chiefly Crohn's disease and ulcerative colitis. Both involve a misdirected immune response against the gut, causing relapsing and remitting symptoms over a lifetime. IBD is common in the UK: around 540,000 people are estimated to live with Crohn's or colitis, equivalent to roughly 1 in 123 people, and prevalence has risen steadily over recent decades. It can begin at any age but is most often diagnosed between the teens and forties. The cause is multifactorial, combining inherited genetic susceptibility with environmental influences including smoking, diet, early-life antibiotic exposure and the composition of the gut microbiome. There is no cure, but modern treatments can control inflammation well, and the condition carries a meaningful burden on quality of life, work and NHS resources.
Symptoms & clinical features
Symptoms depend on which part of the gut is affected and how active the inflammation is. Common features include persistent or bloody diarrhoea, abdominal pain and cramping, urgency, unintended weight loss, fatigue and, in Crohn's disease, mouth ulcers or problems around the anus. Crohn's can affect any part of the digestive tract, while ulcerative colitis is confined to the large bowel. Some people also experience inflammation beyond the gut, affecting the joints, skin or eyes. Symptoms typically come and go in flares followed by periods of remission. Importantly, a person's polygenic risk score does not change how the condition presents or feels: the symptoms, severity and disease course are driven by the active inflammation itself, not by the genetic score, which only estimates the likelihood of developing IBD in the first place.
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Affected organs
IBD primarily affects the gastrointestinal tract. Crohn's disease can involve any part of the digestive system from mouth to anus, while ulcerative colitis is limited to the colon and rectum. Inflammation can also extend beyond the gut, causing problems in the joints, skin, eyes and liver, reflecting the systemic nature of the underlying immune dysregulation.
Risks & severity
A polygenic risk score is typically reported as a percentile, showing where you sit relative to others, or as a relative risk compared with someone of average genetic risk. Being in a high percentile means a higher likelihood of developing IBD over a lifetime, but it is a probability, not a certainty: most people even at the upper end never develop the condition, and the score says nothing about how mild or severe any disease would be. Predictive performance varies by condition and, critically, by ancestry. Most large IBD genetic studies were carried out in people of European descent, so scores are generally less accurate for those of African, South Asian, East Asian or other backgrounds. A score is best understood as a refinement of background risk, not a verdict.
Genetic causes
IBD is one of the most extensively studied complex diseases in genetics. Genome-wide association studies have identified more than 240 susceptibility loci, the great majority of which are common variants that each raise risk only slightly. The strongest and most consistently replicated include NOD2 (the first Crohn's disease gene identified) and IL23R, alongside ATG16L1, IRGM, CARD9, PTPN2, TNFSF15 and PRDM1, among many others. These genes cluster in biological pathways that make clear sense for IBD: innate immune sensing of gut bacteria, autophagy (the cell's recycling and bacterial-clearance machinery), the IL-23/Th17 inflammatory axis and maintenance of the intestinal barrier. No single variant is sufficient to cause disease; rather, it is the accumulation of many small-effect alleles, interacting with environmental triggers and the microbiome, that shifts a person towards inflammation. A polygenic score aggregates these many variants into one number.
Inheritance pattern
IBD does not follow simple Mendelian inheritance. Instead of one gene passing down in a predictable pattern, susceptibility is shaped by hundreds of common variants inherited from both parents, each contributing a tiny fraction of risk. The combined effect spreads across the population as a continuous bell-shaped distribution: most people sit near the middle, while smaller numbers fall at the lower and higher ends. Having a close relative with IBD does raise your own risk, reflecting the variants shared within families, but most people with a high genetic load never develop the condition, and many who do have no family history. This is why IBD is described as polygenic and complex. Genes set the background level of susceptibility; environmental factors then determine whether disease actually emerges.
Diagnosis & testing
A polygenic risk score is not a diagnosis. It is a statistical estimate of inherited susceptibility, generated by genotyping many common variants across the genome and weighting each by its effect size to produce a single score, usually expressed as a percentile relative to a reference population. It cannot tell you whether you have IBD, when you might develop it, or how severe it would be. A genuine diagnosis of Crohn's disease or ulcerative colitis is made clinically, by a gastroenterology team assessing symptoms and using blood tests, stool tests such as faecal calprotectin, endoscopy (colonoscopy) and biopsy of the gut lining, sometimes supported by imaging. Polygenic risk should be read as one piece of background information that may inform awareness and conversations with a clinician, never as a substitute for proper medical investigation.
Management & lifestyle
There is no proven way to prevent IBD, but people with elevated polygenic risk can act sensibly on modifiable factors and stay alert to early symptoms. Smoking is the most clearly established lifestyle factor, but its effect differs between the two main forms: smoking substantially increases the risk of, and worsens the course of, Crohn's disease, whereas it is paradoxically associated with a lower risk and milder course of ulcerative colitis (which is more often a disease of non-smokers and ex-smokers). Because smoking carries large harms to the heart, lungs and many cancers, it is never recommended as a way to manage IBD risk, and stopping smoking remains the right advice for everyone, including the protection it offers against Crohn's disease. A varied diet, maintaining a healthy weight, and discussing antibiotic use with a clinician are reasonable general steps, though no specific diet is proven to prevent IBD. The most valuable response to a higher score is vigilance: persistent changes in bowel habit, blood in the stool, ongoing abdominal pain, unexplained weight loss or fatigue should prompt a timely GP visit rather than being dismissed as irritable bowel syndrome. Early specialist assessment and prompt treatment of confirmed IBD reduce complications. People already diagnosed are managed by NHS gastroenterology teams with medicines that calm inflammation, alongside monitoring and, where needed, surgery.
UK care pathway
There is no national NHS screening programme for IBD; the condition is identified when people present with symptoms. Typically a GP assesses persistent bowel symptoms and, following NICE guidance, uses a faecal calprotectin stool test to help distinguish likely inflammation from irritable bowel syndrome. A raised result, or red-flag features such as rectal bleeding or weight loss, leads to referral to hospital gastroenterology for colonoscopy and biopsy to confirm the diagnosis. Confirmed IBD is then managed by specialist teams. Polygenic scores currently sit outside this NHS pathway.
Frequently asked questions
How is polygenic IBD risk different from a single faulty gene?
A single-gene (monogenic) fault, like those behind some rare very-early-onset IBD in children, is one powerful change that largely determines disease on its own and follows a predictable inheritance pattern. Polygenic risk is the opposite: it is the combined effect of hundreds of common variants, each adding only a tiny amount. No single one causes IBD; it is the total load, plus environment and the gut microbiome, that shifts your susceptibility. That is why a polygenic score gives a probability across a continuous range rather than a yes-or-no answer.
Is a polygenic risk score for IBD available on the NHS?
No. The NHS does not currently offer polygenic risk scoring for IBD, and there is no national screening programme. NHS care begins when symptoms appear: your GP can arrange a faecal calprotectin stool test and, if needed, refer you to gastroenterology for colonoscopy. Polygenic scores are available privately and are best viewed as background information to discuss with a clinician, not as a diagnostic test or a replacement for NHS assessment.
If my polygenic score is high, will I definitely get Crohn's or colitis?
No. A high score means a higher-than-average chance over your lifetime, not a certainty. Most people even at the top end of the distribution never develop IBD, because genes set background susceptibility while environmental factors such as smoking determine whether disease actually emerges. The score also cannot predict how mild or severe any future disease would be. Treat a high score as a reason to stay aware of gut symptoms and seek prompt assessment, not as a diagnosis.
Does my ancestry affect how accurate the score is?
Yes, and it matters. Most of the large genetic studies underpinning IBD polygenic scores were conducted in people of European descent. As a result, scores tend to be most accurate for European-ancestry individuals and less reliable for people of African, South Asian, East Asian or mixed backgrounds. This is a recognised limitation across polygenic scores generally, so the score should be interpreted with your ancestry in mind and never treated as equally precise for everyone.
References
- Singh N, Bernstein CN. Environmental risk factors for inflammatory bowel disease. United European gastroenterology journal. 2022. PMID: 36262056
- Svolos V, Gordon H, Lomer MCE. European Crohn's and Colitis Organisation consensus on dietary management of inflammatory bowel disease. Journal of Crohn's & colitis. 2025. PMID: 40650933
- Yu YR, Rodriguez JR. Clinical presentation of Crohn's, ulcerative colitis, and indeterminate colitis: Symptoms, extraintestinal manifestations, and disease phenotypes. Seminars in pediatric surgery. 2017. PMID: 29126502
- Yang QH, Zhang CN. Comparative study on the pathogenesis of Crohn's disease and ulcerative colitis. World journal of gastroenterology. 2025. PMID: 40497094
- Katsandegwaza B, Horsnell W, Smith K. Inflammatory Bowel Disease: A Review of Pre-Clinical Murine Models of Human Disease. International journal of molecular sciences. 2022. PMID: 36012618
- Gaidos JKJ, Hashash JG. Monitoring Inflammatory Bowel Disease Activity: When, How, and Why. The American journal of gastroenterology. 2025. PMID: 40488637
- Varma P, Falconer J, Aga A. Rituximab-induced Crohn's disease. Scandinavian journal of gastroenterology. 2017. PMID: 28129697
- Sturm A, Maaser C, Mendall M. European Crohn's and Colitis Organisation Topical Review on IBD in the Elderly. Journal of Crohn's & colitis. 2017. PMID: 27797918