IBS Genetics: What You Need To Know

Published on Wednesday, July 05, 2023 by Elyse Krawtz

Have you ever wondered whether you inherited your IBS from your parents?

According to a large Nature Genetics study in 2021 that completed a genome-wide analysis of 53,400 people with IBS, IBS genetic heritability is modest even though people with a relative with IBS are two-to-three times more likely to develop IBS.

How is that possible? Yes, you inherit genes from your parents…but that isn’t all you inherit.

Families share food, stress, lifestyle habits, vacations, living environment, and sometimes even infections. Lower genetic heritability means that these--diet, stress, learned behaviors, and dysbiosis--are likely more critical in IBS than genetic factors.

However, the authors did find six genetic associations with IBS. The strongest associations were NOT overlapping with gastrointestinal conditions like inflammatory bowel disease or celiac disease, but rather, with mood and anxiety disorders. According to the National Center for Biotechnology Information (NCBI), some identified genes also have immune roles.

These are the six genes identified as implicated in IBS:

NCAM1 plays a role in cell growth, cell-to-cell interactions and neural adhesion, antiviral response, immune surveillance, and immune cell movement. The authors note it is associated with neuroticism, depression, cannabis use, and anorexia nervosa, and though mainly expressed in the brain, it can be in the gut.
CADM2 plays a role in neural adhesion and is mainly expressed in the brain, not the gut; according to the authors, CADM2 has been associated with neuroticism, anxiety, and cannabis use.
PHF2/FAM120A has been associated with neuroticism, depression, and autism; it plays a role in brain development and can be in the brain and gut, according to the authors.
DOCK9 is important for brain development but can also be expressed in the gut nerves, according to the authors.
CKAP2/TPTE2P3 plays a role in cell division and is expressed in many tissues that manufacture new cells, such as the immune tissues (bone marrow and lymph nodes) and the testis.
BAG6 plays many roles, some cell-cycle related and some immune-related. Although it is located near genes associated with celiac disease, ulcerative colitis, and microscopic colitis, it was independent of those associated with the other genetic conditions, according to the authors.

What does this mean for someone with IBS? This strengthens the gravity of the gut-brain connection: changes in the genes involved in nerve cell functioning could influence IBS risk.

So, do you need genome sequencing for IBS? Genetic sequencing is unlikely to influence treatment, while scientists are still exploring IBS genetics to develop targeted therapies and precision interventions for individuals. Even when IBS genetics are better understood, environmental factors are still going to play a significant role in IBS.

Environment remains important for people with IBS. That means everything besides the genes you were born with: nutrition, sleep, exercise, social relationships, living space, travel, community, stress, sleep schedule, medications, gut microbiota, and more.
Make mental health a priority. It is hard to over-emphasize the “gut-brain connection” in IBS. Talk to your doctor about mental health screening and support that is right for you, especially if you are struggling with anxiety and/or depressive symptoms.
Don’t sleep on getting help for insomnia. Regardless of whether insomnia triggers IBS or IBS triggers insomnia, insomnia is not okay to ignore because insufficient sleep harms your cardiometabolic, immune, and mental health. Ask your doctor about insomnia diagnosis and treatment options, including non-pharmacological options such as cognitive behavioral therapy for insomnia.
Your personality could matter in IBS. According to the American Psychological Association, neuroticism is a chronic level of emotional instability and proneness to psychological distress. Neuroticism may increase vulnerability to health problems, interfere with recovery and healing, and increase the risk of substance abuse, according to authors in World Psychiatry. If you struggle with neuroticism, advocate for the support you need by talking to your doctor and working with a qualified therapist.
Mind your immune system. There is still a LOT to learn about exactly what and how immune-related genes influence IBS. But a balanced and equipped immune system is better than the alternative. Nourish your immune system with a healthy diet, and talk with your doctor about whether you are experiencing any signs of chronic inflammation or immune deficits.

_{Eijsbouts, C., Zheng, T., Kennedy, N. A., Bonfiglio, F., Anderson, C. A., Moutsianas, L., Holliday, J., Shi, J., Shringarpure, S., 23andMe Research Team, Voda, A. I., Bellygenes Initiative, Farrugia, G., Franke, A., Hübenthal, M., Abecasis, G., Zawistowski, M., Skogholt, A. H., Ness-Jensen, E., Hveem, K., … Parkes, M. (2021). Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders. Nature genetics, 53(11), 1543–1552. https://doi.org/10.1038/s41588-021-00950-8}
_{U.S. National Library of Medicine. (2023, March 29). NCAM1 neural cell adhesion molecule 1 [homo sapiens (human)] - gene - NCBI. National Center for Biotechnology Information. Retrieved April 28, 2023, from https://www.ncbi.nlm.nih.gov/gene/4684}
_{U.S. National Library of Medicine. (2023, March 29). Cadm2 cell adhesion molecule 2 [homo sapiens (human)] - gene. National Center for Biotechnology Information. Retrieved April 28, 2023, from https://www.ncbi.nlm.nih.gov/gene/253559}
_{U.S. National Library of Medicine. (2023, April 4). PHF2 Phd finger protein 2 [homo sapiens (human)] - gene. National Center for Biotechnology Information. Retrieved April 28, 2023, from https://www.ncbi.nlm.nih.gov/gene/5253}
_{U.S. National Library of Medicine. (2023, April 9). FAM120A family with sequence similarity 120A [homo sapiens (human)] - gene. National Center for Biotechnology Information. Retrieved April 28, 2023, from https://www.ncbi.nlm.nih.gov/gene/23196}
_{U.S. National Library of Medicine. (2023, March 29). Dock9 dedicator of cytokinesis 9 [homo sapiens (human)] - gene. National Center for Biotechnology Information. Retrieved April 28, 2023, from https://www.ncbi.nlm.nih.gov/gene/23348}
_{U.S. National Library of Medicine. (2023, March 29). CKAP2 cytoskeleton associated protein 2 [homo sapiens (human)] - gene. National Center for Biotechnology Information. Retrieved April 28, 2023, from https://www.ncbi.nlm.nih.gov/gene/26586}
_{U.S. National Library of Medicine. (2023, March 29). Bag6 bag cochaperone 6 [homo sapiens (human)] - gene. National Center for Biotechnology Information. Retrieved April 28, 2023, from https://www.ncbi.nlm.nih.gov/gene/7917}
_{Rossman J. (2019). Cognitive-Behavioral Therapy for Insomnia: An Effective and Underutilized Treatment for Insomnia. American journal of lifestyle medicine, 13(6), 544–547. https://doi.org/10.1177/1559827619867677}
_{American Psychological Association. (n.d.). Neuroticism. APA Dictionary of Psychology. Retrieved April 28, 2023, from https://dictionary.apa.org/neuroticism}
_{Widiger, T. A., & Oltmanns, J. R. (2017). Neuroticism is a fundamental domain of personality with enormous public health implications. World psychiatry : official journal of the World Psychiatric Association (WPA), 16(2), 144–145. https://doi.org/10.1002/wps.20411}