Elucidating the causal links between plasma and cerebrospinal fluid metabolites and pituitary tumors: a Mendelian randomization analysis

Abstract

BackgroundPituitary tumors (PTs) are common benign intracranial tumors. Investigating the metabolites in serum and cerebrospinal fluid in PTs is essential to understanding the underlying biological mechanisms and identifying new biomarkers and therapeutic strategies.MethodsWe used the GWAS dataset of PTs from the FinnGen database, a dataset of 486 plasma metabolites from the GWAS catalog database, and a dataset of 338 cerebrospinal fluid (CSF) metabolites from the WADRC and WRAP study collections. An inverse variance weighting (IVW) approach was utilized as the mainly method to investigate causality between metabolites and PTs, supplemented by four complementary methods to strengthen our findings. Additionally, we utilized several sensitivity methods to guarantee the robustness of our findings.ResultsThe study identified 17 plasma metabolites and 10 CSF metabolites related to PTs. Among these, 11 metabolites indicated a significant positive causality with PTs, while 16 displayed a remarkable negative causality. Particularly, plasma levels of 3-dehydrocarnitine (OR = 2.73, 95% CI = 1.55–4.83, P = 0.001) and acetylcarnitine (OR = 0.35, 95% CI = 0.19–0.63, P = 0.001) were found to be significant exposure factors for PTs. Multiple sensitivity analyses confirm the robustness of the results. The study found no evidence of a reverse causality between PTs and the plasma levels of 3-dehydrocarnitine and acetylcarnitine.ConclusionsThe present study identified 27 metabolites associated with the incidence of PTs, among which 3-dehydrocarnitine and acetylcarnitine are the most noteworthy.