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

Evidence for causal associations between functional dyspepsia (FD) and human metabolites remains limited. Two-sample and multivariable Mendelian randomizations to detect the causal relationships between FD and human metabolites. Single nucleotide polymorphisms significantly associated with human metabolites were selected as instrumental variables, the inverse variance weighting method was used as the primary analysis method, and the results were tested for heterogeneity and horizontal pleiotropy. Genetically predicted levels of 26 circulating metabolites and 5 cerebrospinal fluid metabolites were associated with FD. Among them, Total cholesterol in large low-density lipoprotein (odds ratio [OR] = 0.985, 95% confidence interval [CI] 0.975–0.995, P  = .003) and cholesteryl esters to total lipids ratio in intermediate-density lipoprotein (OR = 0.983, 95% CI 0.971–0.996, P  = .008) were negatively associated with FD. It was also positively associated with the level of phenylalanine (OR = 1.037, 95% CI 1.009–1.065, P  = .009) and phospholipids to total lipids ratio in small high-density lipoprotein (OR = 1.015, 95% CI 1.003–1.027, P  = .017). After multivariable adjustment, FD was causally associated with phospholipids to total lipids ratio in small high-density lipoprotein (OR = 1.332, 95% CI 1.060–1.674, P  = .014). Sensitivity analyses showed no evidence of heterogeneity and horizontal pleiotropy in the above results. Human metabolites may be associated with FD.