Causal associations between human metabolites and functional dyspepsia: Evidence from two sample and multivariable...

Area of Science:

• Metabolomics
• Gastroenterology
• Human Genetics

Background:

• Functional dyspepsia (FD) is a common gastrointestinal disorder with limited understanding of its underlying causes.
• The causal relationship between human metabolites and FD remains largely unexplored.
• Investigating metabolic profiles may reveal novel insights into FD pathophysiology.

Purpose of the Study:

• To investigate the potential causal associations between human metabolites and functional dyspepsia (FD).
• To identify specific metabolites that are causally linked to the risk or presence of FD.
• To utilize advanced genetic methods to establish causality.

Main Methods:

• Employed two-sample and multivariable Mendelian randomization (MR) analyses.
• Utilized single nucleotide polymorphisms (SNPs) associated with human metabolites as instrumental variables.
• Applied inverse variance weighting (IVW) as the primary MR method, with sensitivity analyses for heterogeneity and pleiotropy.

Main Results:

• Genetically predicted levels of 26 circulating and 5 cerebrospinal fluid metabolites were associated with FD.
• Negative associations were observed for total cholesterol in large LDL and cholesteryl esters in intermediate-density lipoprotein.
• Positive associations were found for phenylalanine and phospholipids to total lipids ratio in small HDL, with the latter showing a significant causal link after multivariable adjustment.

Conclusions:

• Human metabolites, particularly phospholipids to total lipids ratio in small HDL, are causally associated with functional dyspepsia.
• These findings suggest that metabolic dysregulation may play a role in the development of FD.
• Further research into metabolic pathways could lead to novel therapeutic targets for FD.