Multi-omics Mendelian randomization of predefined inflammation- and immunity-related genes reveals causal candidates for neurogenic bladder dysfunction
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background Inflammatory and immune pathways have been implicated in neurogenic bladder dysfunction (NBD), but the causal contribution of predefined inflammation- and immunity-related genes to NBD remains incompletely understood. The aim of this study was to analyse the causal relationship between inflammation/immunity-related genes and NBD based on multi-omics Mendelian randomisation (MR).Methods We analysed genome-wide association studies (GWAS), expression quantitative trait loci (eQTL) and methylation quantitative trait loci (mQTL) data using SMR analysis and tested the robustness of the results by the heterogeneity in dependent instruments (HEIDI) test.Results The three-step SMR analysis showed that four DNA methylation (DNAm) sites and three genes regulated by them were associated with genetic liability to NBD. cg14544641-regulated SEMA4D was negatively associated with the risk of NBD, interpreted as genetic liability to NBD in this summary-level GWAS context (beta = –0.214; p = 0.014). cg10564498- and cg03247049-regulated AXL were positively associated with the risk of NBD (beta = 0.432; p = 0.034). cg21601405-regulated CD40 was positively associated with the risk of NBD (beta = 0.116; p = 0.047).Conclusions The present study demonstrates three predefined inflammation/immunity-related genes and four DNAm sites with potential causal associations with genetic liability to NBD. These findings may help prioritise molecular mechanisms, biomarkers, and target-discovery work relevant to NBD prevention and management, although validation in bladder-specific and disease-specific experimental models is required before clinical or public health translation.
Source: Critical Public Health
Authors: Juan Zhao, Jian Cai
Institution: Chengdu University of Traditional Chinese Medicine
Language: English
Subfield: Urology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7203756959