Causal association between circulating Klotho levels and B-cell lymphoma: A 2-sample Mendelian randomization study

This study aimed to investigate a causal association between Klotho levels and the risk of B-cell lymphoma using a Mendelian randomization (MR) approach. We sought to determine if α-Klotho levels are causally linked to various subtypes of B-cell lymphoma, including diffuse large B-cell lymphoma, follicular lymphoma, Hodgkin lymphoma, and non-Hodgkin lymphoma. We obtained GWAS data for B-cell lymphomas from the FINN Large Cohort in the IEU database and α-Klotho levels from a meta-analysis of GWAS data. The primary analysis employed the inverse-variance weighted method, while sensitivity analyses utilized weighted median, MR-Egger, and weighted mode methods to validate results. Heterogeneity and pleiotropy of genetic instruments were assessed using leave-one-out sensitivity tests, the MR pleiotropy residual sum and outlier test (MR-PRESSO), and Cochran Q test. Our analysis revealed no significant associations between α-Klotho levels and any subtype of B-cell lymphoma using inverse-variance weighted (IVW). The odds ratios and 95% confidence intervals indicated no significant relationship for diffuse large B-cell lymphoma, follicular lymphoma, Hodgkin lymphoma, or unspecified non-Hodgkin lymphoma. Heterogeneity tests and sensitivity analyses supported the robustness of these findings. Our comprehensive MR analysis suggests no causal relationship exists between Klotho levels and the risk of developing B-cell lymphomas.