Exploring the causal relationship between constipation and ileus: Insights from bidirectional Mendelian randomization...

Area of Science:

• Gastroenterology and Genetics
• Investigating the complex interplay between functional gastrointestinal disorders and surgical emergencies.

Background:

• Constipation affects 15% globally, with increasing incidence due to modern lifestyles.
• Ileus, a surgical emergency, often co-occurs with constipation, but their relationship is poorly understood.

Purpose of the Study:

• To elucidate the causal relationship and underlying molecular mechanisms connecting constipation and ileus.
• To identify shared genetic factors and biochemical pathways involved in the development of both conditions.

Main Methods:

• Bidirectional 2-sample Mendelian randomization (MR) analysis using the IEU OpenGWAS database.
• Identification of co-expressed genes via eQTL datasets and pathway analysis using Gene Ontology, KEGG, and GeneMANIA.
• Construction of protein-protein interaction (PPI) networks to pinpoint key molecular players.

Main Results:

• MR analysis demonstrated a significant causal link between constipation and an elevated risk of ileus (OR=1.467, P<.001).
• Six genes were found to be co-expressed in both constipation and ileus.
• Enrichment analyses implicated nucleic acid metabolism and ribosomal biosynthesis, with UPB1 identified as a key gene.

Conclusions:

• Constipation and ileus share a causal relationship with significant underlying genetic susceptibility.
• Biochemical pathways, including nucleic acid metabolism and ribosomal biosynthesis, may mediate the link, with UPB1 as a potential therapeutic target.
• This study provides novel insights into the genetic basis of constipation and ileus, paving the way for targeted interventions.