ArticleGenome medicine2023
Shared genetic architecture between irritable bowel syndrome and psychiatric disorders reveals molecular pathways of the gut-brain axis.
Article in Genome medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Pooled it
- Associations between childhood behavior and current cognitive and emotional function in adults with irritable bowel syndrome-a cross sectional retrospective study.BMC gastroenterology · 2026Observational
- A lesion-derived brain network of somatic symptoms for transdiagnostic individual application.BMC medicine · 2026Article
- Phocaeicola vulgatus improves anxiety-like behavior by ameliorating amygdala neuroinflammation and the neurite impairment in IBS.Translational psychiatry · 2026Article
- Residential green space mitigates genetic susceptibility to incident irritable bowel syndrome in a prospective cohort of 376 749 individuals.Journal of global health · 2026Article
- Shared Genetic Liability across Systems of Psychiatric and Physical Illness.Nature communications · 2026Article
- Large-scale meta- and cross-trait analyses uncover shared genetic risk factors for IBS and psychiatric disorders.Frontiers in psychiatry · 2026Article
- Pathophysiological Mechanisms and Nonpharmacological Interventions in Irritable Bowel Syndrome: Current Insights and Future Directions.Journal of nutrition and metabolism · 2026Review
- Neuroimmune Crossroads: Pathophysiological Links Between Bipolar Disorder and Inflammatory Bowel Disease.Actas espanolas de psiquiatria · 2025Review
- Shared Genetic Architecture and Neurobiological Pathways of Problematic Alcohol Use and Anxiety Disorders.medRxiv : the preprint server for health sciences · 2025Article
- Distinct patterns of genetic overlap among multimorbidities revealed with trivariate MiXeR.Genome medicine · 2025Article
- Genomic relationship between polycystic ovary syndrome and bipolar disorder.Research square · 2025Article
- Genome-wide analysis identifies novel shared loci between depression and white matter microstructure.Molecular psychiatry · 2025Article
- Familial coaggregation and shared familiality of functional and internalizing disorders in the Lifelines cohort.Psychological medicine · 2025Article
- Alcohol use disorder and body mass index show genetic pleiotropy and shared neural associations.Nature human behaviour · 2025Article
- Enhanced insights into the genetic architecture of 3D cranial vault shape using pleiotropy-informed GWAS.Communications biology · 2025Article
- Should we consider microbiota-based interventions as a novel therapeutic strategy for schizophrenia? A systematic review and meta-analysis.Brain, behavior, & immunity - health · 2025Article
- Anxiety and Depression Disorders in Vietnamese Patients With Irritable Bowel Syndrome: A Cross-Sectional Clinic-Based Study.JGH open : an open access journal of gastroenterology and hepatology · 2025Article
- Systematic dissection of pleiotropic loci and critical regulons in excitatory neurons and microglia relevant to neuropsychiatric and ocular diseases.Translational psychiatry · 2025Article
- Integrating genetics and transcriptomics to characterize shared mechanisms in digestive diseases and psychiatric disorders.Communications biology · 2025Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 3 countries.
Funding
Abstract
backgroundIrritable bowel syndrome (IBS) often co-occurs with psychiatric and gastrointestinal disorders. A recent genome-wide association study (GWAS) identified several genetic risk variants for IBS. However, most of the heritability remains unidentified, and the genetic overlap with psychiatric and somatic disorders is not quantified beyond genome-wide genetic correlations. Here, we characterize the genetic architecture of IBS, further, investigate its genetic overlap with psychiatric and gastrointestinal phenotypes, and identify novel genomic risk loci.
methodsUsing GWAS summary statistics of IBS (53,400 cases and 433,201 controls), and psychiatric and gastrointestinal phenotypes, we performed bivariate casual mixture model analysis to characterize the genetic architecture and genetic overlap between these phenotypes. We leveraged identified genetic overlap to boost the discovery of genomic loci associated with IBS, and to identify specific shared loci associated with both IBS and psychiatric and gastrointestinal phenotypes, using the conditional/conjunctional false discovery rate (condFDR/conjFDR) framework. We used functional mapping and gene annotation (FUMA) for functional analyses.
resultsIBS was highly polygenic with 12k trait-influencing variants. We found extensive polygenic overlap between IBS and psychiatric disorders and to a lesser extent with gastrointestinal diseases. We identified 132 independent IBS-associated loci (condFDR < 0.05) by conditioning on psychiatric disorders (n = 127) and gastrointestinal diseases (n = 24). Using conjFDR, 70 unique loci were shared between IBS and psychiatric disorders. Functional analyses of shared loci revealed enrichment for biological pathways of the nervous and immune systems. Genetic correlations and shared loci between psychiatric disorders and IBS subtypes were different.
conclusionsWe found extensive polygenic overlap of IBS and psychiatric and gastrointestinal phenotypes beyond what was revealed with genetic correlations. Leveraging the overlap, we discovered genetic loci associated with IBS which implicate a wide range of biological pathways beyond the gut-brain axis. Genetic differences may underlie the clinical subtype of IBS. These results increase our understanding of the pathophysiology of IBS which may form the basis for the development of individualized interventions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.