Genetics of irritable bowel syndrome: shifting gear via biobank-scale studies

Camilleri, Michael; Zhernakova, Alexandra; Bozzarelli, Isotta; D’Amato, Mauro

doi:10.1038/s41575-022-00662-2

Cited by 20 publications

(23 citation statements)

References 200 publications

(231 reference statements)

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“…[39][40][41][42] Finally, whilst beyond the remit of the current study, there is increasing interest in genetic factors, which may be involved in predisposition to DGBI. 43 It is unclear whether genetic variance could account for some of the observed differences in DGBI prevalence between the UK and the other countries in our study. Future global population studies are warranted to determine the effects of genetic variance on DGBI prevalence.…”

Section: Discussionmentioning

confidence: 78%

“…Whilst this could not be explored further within our study, this is an important area for future research especially in countries with multiethnic, multicultural populations such as the UK, where there is a an increasing recognition of the need to prevent racial disparities in order to unify the approach to the diagnosis and treatment of DGBI 39–42 . Finally, whilst beyond the remit of the current study, there is increasing interest in genetic factors, which may be involved in predisposition to DGBI 43 . It is unclear whether genetic variance could account for some of the observed differences in DGBI prevalence between the UK and the other countries in our study.…”

Section: Discussionmentioning

confidence: 92%

See 1 more Smart Citation

The national prevalence of disorders of gut brain interaction in the United Kingdom in comparison to their worldwide prevalence: Results from the Rome foundation global epidemiology study

Jaafari

Houghton

West

et al. 2023

Neurogastroenterology Motil

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Background: There are minimal epidemiological data comparing the burden of disorders of gut brain interaction (DGBI) in the UK with other countries. We compared the prevalence of DGBI in the UK with other countries that participated in the Rome Foundation Global Epidemiology Study (RFGES) online. Methods:Participants from 26 countries completed the RFGES survey online including the Rome IV diagnostic questionnaire and an in-depth supplemental questionnaire with questions about dietary habits. UK sociodemographic and prevalence data were compared with the other 25 countries pooled together.The Rome Foundation Global Epidemiological Study (RFGES) spanning six continents provided the most comprehensive worldwide data on the prevalence of all 22 Rome IV disorders of gut-brain interaction (DGBI). 1 The global prevalence of these disorders was found to be high, with 40.3% of participants meeting criteria for at least one DGBI. 1 Aside from the overall global prevalence of DGBI and their interactions and overlap, the original study has, importantly, captured data on the burden and impact of these conditions with data on healthcare utilization and impact on quality-of-life worldwide. These data have not only been important in raising awareness of just how prevalent DGBI are on a worldwide scale but have also provided unique opportunities to understand how the prevalence of DGBI may vary amongst countries, and examining sociodemographic factors that may contribute to epidemiological differences, including dietary practices. The first country-level analysis of the RFGES dataset provided detailed national prevalence data for all 22 DGBIs in Israel, and compared the prevalence, healthcare utilization, and quality-of-life data with the other 25 countries that completed the questionnaire using the same Internet-based methodology. 2 However, to our knowledge, no studies have previously compared the epidemiology of DGBI in the UK with their epidemiology worldwide.In the UK, despite DGBI accounting for a significant proportion of gastroenterology outpatient workload, 3 and substantial direct financial costs estimated to be between £1.3 and £2 billion for irritable bowel syndrome (IBS) alone, 4 these chronic disorders are given low priority in the gastroenterology training curriculum, 5-7 are of limited priority for research funding, 8 and there are only a few specialized centers nationally that offer integrated multidisciplinary care for DGBI, despite this being recognized increasingly as the standard of care. 9 Recently updated evidence-based national DGBI guidelines from the British Society of Gastroenterology on IBS and functional dyspepsia (FD) have emphasized the role of making positive diagnoses, and use of sequential first-, second-, and third-line therapies,

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 92%

The national prevalence of disorders of gut brain interaction in the United Kingdom in comparison to their worldwide prevalence: Results from the Rome foundation global epidemiology study

Jaafari

Houghton

West

et al. 2023

Neurogastroenterology Motil

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“…Preclinical and clinical studies investigating genetic determinants of pain and visceral sensation have focused largely on identifying genetic variations associated with immune dysregulation, barrier function, neurotransmitter biosynthesis and metabolism, cannabinoid receptors, ion channel dysfunction, and G-protein coupled receptor expression alongside other mechanisms. 27 , 149 The increasing availability of large-scale population-based biobanks have facilitated advancements in genomic research in IBS 150 that may accelerate our understanding of genetic risk determinants in IBS. In one genome-wide association study of 53,400 people with IBS, six genes ( NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6 ) were found to be associated with IBS susceptibility including four genes linked to mood, anxiety, or expressed in the nervous system.…”

Section: Omics-based Biomarkers For Abdominal Pain In Ibsmentioning

confidence: 99%

Multi-omics for biomarker approaches in the diagnostic evaluation and management of abdominal pain and irritable bowel syndrome: what lies ahead

Shin

Kashyap

2023

Gut Microbes

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Reliable biomarkers for common disorders of gut–brain interaction characterized by abdominal pain, including irritable bowel syndrome (IBS), are critically needed to enhance care and develop individualized therapies. The dynamic and heterogeneous nature of the pathophysiological mechanisms that underlie visceral hypersensitivity have challenged successful biomarker development. Consequently, effective therapies for pain in IBS are lacking. However, recent advances in modern omics technologies offer new opportunities to acquire deep biological insights into mechanisms of pain and nociception. Newer methods for large-scale data integration of complementary omics approaches have further expanded our ability to build a holistic understanding of complex biological networks and their co-contributions to abdominal pain. Here, we review the mechanisms of visceral hypersensitivity, focusing on IBS. We discuss candidate biomarkers for pain in IBS identified through single omics studies and summarize emerging multi-omics approaches for developing novel biomarkers that may transform clinical care for patients with IBS and abdominal pain.

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“…The pathogenesis of IBS is complex and recent studies bring the consensus that IBS mainly results from the disorder of gut–brain interactions [ 2 ]. Furthermore, epidemiological studies suggest that genetics, diet, gut microbiota dysbiosis, gut infection, and psychological factors are all risk factors for IBS, which can exert effects on IBS via disrupting the bidirectional interactions of the gut–brain axis [ 3 , 4 ]. Considering these factors, the common therapeutics for IBS include dietary exclusion, probiotics/fecal microbiota transplant, antibiotics, psychotropic medications, and symptom-relieving drugs (e.g., antispasmodics, antidiarrheal agents, and laxative) [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Calcium, 25-Hydroxyvitamin D, and Parathyroid Hormone in Irritable Bowel Syndrome: A Bidirectional Two-Sample Mendelian Randomization Study

Xie

Wang

et al. 2022

Nutrients

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Several observational studies have indicated the potential associations among calcium, vitamin D (Vit-D), and irritable bowel syndrome (IBS). However, the causal relationship deduced from these studies is subject to residual confounding factors and reverse causation. Therefore, we aimed to explore the bidirectional causal effects among serum calcium, Vit-D, PTH, and IBS at the genetic level by a two-sample Mendelian randomization (MR) analysis of the datasets from IEU OpenGWAS database. Sensitivity analyses were performed to evaluate the robustness. The estimates were presented as odds ratios (ORs) with their 95% confidence intervals (CIs). The results of the inverse variance weighted method did not reveal any causal relationship between the genetically predisposed calcium (OR = 0.92, 95% CI: 0.80–1.06, p = 0.25) and Vit-D (OR = 0.99, 95% CI: 0.83–1.19, p = 0.94) level and the risk of IBS. The bidirectional analysis demonstrated that genetic predisposition to IBS was associated with a decreased level of PTH (beta: −0.19, 95%CI: −0.34 to −0.04, p = 0.01). In conclusion, the present study indicates no causal relationship between the serum calcium and Vit-D concentrations and the risk of IBS. The potential mechanisms via which IBS affects serum PTH need to be further investigated.

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Genetics of irritable bowel syndrome: shifting gear via biobank-scale studies

Abstract: Nature reviews | GastroenteroloGy & HepatoloGy 0123456789();: PrevalenceThe proportion of individuals in a population who have a specific characteristic (typically a disease) at a specific time.

Cited by 20 publications

References 200 publications

The national prevalence of disorders of gut brain interaction in the United Kingdom in comparison to their worldwide prevalence: Results from the Rome foundation global epidemiology study

The national prevalence of disorders of gut brain interaction in the United Kingdom in comparison to their worldwide prevalence: Results from the Rome foundation global epidemiology study

Multi-omics for biomarker approaches in the diagnostic evaluation and management of abdominal pain and irritable bowel syndrome: what lies ahead

The Role of Calcium, 25-Hydroxyvitamin D, and Parathyroid Hormone in Irritable Bowel Syndrome: A Bidirectional Two-Sample Mendelian Randomization Study

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