GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome, 2021, Bonfiglio et al

Highlights

• Genetics of gut motility via data on stool frequency in 167,875 individuals
• GWAS identifies 14 loci associated with stool frequency
• Candidate genes enriched in neurotransmitter signaling and enteric motor neurons
• Polygenic scores predict increased risk of irritable bowel syndrome

Summary

Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p ≤ 5.0 × 10−8). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndromes and the response to their pharmacological treatment. The genetic architecture of stool frequency correlates with that of IBS, and UK Biobank participants from the top 1% of stool frequency polygenic score distribution were associated with 5× higher risk of IBS with diarrhea. These findings pave the way for the identification of actionable pathological mechanisms in IBS and the dysmotility syndromes.

Open access, https://www.cell.com/cell-genomics/fulltext/S2666-979X(21)00085-9

 

Brief Twitter thread from one of the authors

 

A bit off topic but it will be so good and exciting to have similar data for ME/CFS. To finally know the pathways involved.

 

GWAS stands for genome-wide association study.