Does irritable bowel syndrome run in families?
Let’s face it. We get some of our best and our worst traits from our mothers…in my case it’s the chatterbox gene (I’m calling that good 😊) and my short stature (not so good ☹️).
For many though, it’s a sensitive tummy. It seems that every IBS patient has a family tree littered with rellies that suffered from bloating, gassiness or some form of digestive distress. But does IBS really run in families?
While 10% of IBS cases are a result of a gut infection, new research released this week finds that family history does play a role in determining your chances of developing IBS. 24% of people with IBS have a family member that also suffers from the debilitating condition.
New study results just released
A massive international study led by researchers at Oxford University has found that whilst environment is the most important factor in causing IBS, there is also a small but consistent heritable component to IBS.
Indeed, they have found six genes associated with the chronic gut condition.
The researchers tapped into the UK biobank, a database containing in-depth genetic information from half a million UK participants and a second database, the Bellygenes initiative, to undertake the study.
171,000 people who have their genetic information stored in the UK biobank answered a questionnaire about their digestive health. This included information about a previous diagnosis of IBS and the Rome III diagnostic questions, which when paired with the Bellygenes database allowed researchers to identify 53,400 people with IBS.
By comparing their genetic makeup to 433,201 people in the biobank without IBS, they were able to work out which genes are associated with IBS.
The six genes were NCAM1, CADM2, PHF2/ FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. To check their results the team repeated the approach with the 23andMe database and found consistent results.
What are the IBS genes?
The six IBS-associated genes are expressed (meaning they have an effect) in cells across a number of tissues, with many genes particularly expressed in the brain. For example, NCAM1 and CADM2 code for adhesion molecules that help brain cells stick together and regulate neural circuit formation. PHF2 and DOCK9 also play key roles in brain development.
Whilst you might have expected the genes to be particularly associated with the gut, this finding fits with what we already know about IBS. IBS is commonly thought to be due to disordered interactions between the gut and the brain. It seems like for IBS with a genetic component that disorder starts in the brain rather than the gut.
“IBS aggregates in families, with individuals being two to three times more likely to develop IBS if they have an affected relative”. [Saito et al. 2011]
These genes may also have an effect through changes in the enteric nervous system - the rich network of nerve fibres associated with the gut. NCAM1, PHF2 and DOCK9 are all expressed in the enteric nervous system as well as the brain.
Consistent with the nervous system being more important than the gut itself, the researchers found that IBS does not share genetic roots with other gut conditions (coeliac disease and Crohn’s disease), even though they share common symptoms.
Debunking some myths about IBS
With such a large cohort, the study was able to debunk many myths about IBS.
The researchers found that the same genes that influenced IBS also influence disorders like depression, anxiety and insomnia. They found that anxiety was much more common in the IBS group (43%) than the control group (16%). Careful genetic analysis by the researchers revealed that this wasn’t down to IBS causing anxiety, or anxiety causing IBS. Instead, there seems to be common genetic factors causing both.
This also helps explain why doctors have found that neuromodulators such as tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) can also be used to treat IBS..
They also found that IBS was pretty common – 14% or the respondent to the survey in the UK database met the Rome III criteria. And as we’ve reported before (see our blog), IBS is more common in women than men. In this study 72% of the IBS sufferers were women.
The mixed sub-type of IBS, where people experience both hard and loose stools at least some of the time was the most common subtype (55%).
Only 35% had ever had an official diagnosis from a doctor.
They found that people with more severe IBS symptoms were more likely to suffer from back pain, limb pain and headache.
In terms of possible environmental causes of IBS. They found that people with IBS were more likely to report having had antibiotics as children, but were no more likely to have been born by caesarean, than the comparison group.
Where might this research lead?
The sixth gene identified as being correlated with IBS, BAG6 is part of the immune system. It is involved in a weird and wonderful array of processes including chaperoning misfolded proteins, regulating membrane proteins and presentation of antigens on the surface of cells.
Working out how it plays a role in IBS, may help us understand IBS better and lead to new treatments for the condition.
In the meantime, perhaps take comfort in the fact that there is often at least family member we can turn to for understanding or advice when we are struggling with symptoms.
Ref: Eijsbouts, C., Zheng, T., Kennedy, N.A. et al. Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders. Nat Genet 53, 1543–1552 (2021). https://doi.org/10.1038/s41588-021-00950-8
Saito, Y. A. The role of genetics in IBS. Gastroenterol. Clin. North Am. 40, 45–67 (2011).