Trial Report Shared genetic architecture between irritable bowel syndrome and psychiatric disorders reveals molecular pathways of the gut-brain axis, 2023, Tesfaye

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https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-023-01212-4

• Research
• Open Access
• Published: 01 August 2023

Shared genetic architecture between irritable bowel syndrome and psychiatric disorders reveals molecular pathways of the gut-brain axis

• Markos Tesfaye,
• Piotr Jaholkowski,
• Guy F. L. Hindley,
• Alexey A. Shadrin,
• Zillur Rahman,
• Shahram Bahrami,
• Aihua Lin,
• Børge Holen,
• Nadine Parker,
• Weiqiu Cheng,
• Linn Rødevand,
• Oleksandr Frei,
• Srdjan Djurovic,
• Anders M. Dale,
• Olav B. Smeland,
• Kevin S. O’Connell &
• Ole A. Andreassen

Genome Medicine volume 15, Article number: 60 (2023) Cite this article

Abstract
Background
Irritable 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.

Methods
Using 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.

Results
IBS 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.

Conclusions
We 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.

 

https://www.sciencealert.com/many-of-the-genes-behind-ibs-could-also-affect-our-mental-health

Many of The Genes Behind IBS Could Also Affect Our Mental Health

There are notable genetic correlations between irritable bowel syndrome (IBS), and mental health disorders such as anxiety, depression, bipolar disease, and schizophrenia, a new study reveals.

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On this occasion the researchers didn't look any deeper into any mechanisms related to the genetic overlap, but they suggest intestine inflammation may cause bacteria to leak into the blood and make their way to the brain, which can lead to behavioral and cognitive changes, and might explain the high co-occurrence of IBS with psychiatric disorders.

Scientists are continuing to unpick the way our brains and bellies are linked – from the way that a better education protects your gut, to how certain kinds of bacteria are associated with the development of Alzheimer's.