Bidirectional Mendelian Randomization and Genetic Insights Reveal Causal Relationships Between Cancer and Epilepsy Subtypes
Description
The data that support the findings of this study are available in the IEU OpenGWAS database at https://gwas.mrcieu.ac.uk/. The reference numbers for all datasets are the GWAS IDs compiled in Supplementary Tables 1 and 10. These data were derived from the following resources available in the domain: the complete set of genome-wide association studies, as detailed with their respective consortium names and original publication links in the data sources section of the manuscript.
Files
Steps to reproduce
Genome-wide association study (GWAS) summary data for epilepsies (all-type [AE], generalized [GE], focal [FE]) and 15 cancers were sourced from IEU Open GWSS. Single-nucleotide polymorphisms (SNPs) at genome-wide significance ((P < 5e-08 or 06) served as instruments. Expression quantitative trait loci (eQTLs) analyses explored mediating pathways. Sensitivity analyses included Cochran’s Q and MR-PRESSO. Forward MR linked esophageal adenocarcinoma and neuroblastoma to AE; breast, lung, and invasive mucinous ovarian cancers to GE; esophageal adenocarcinoma, neuroblastoma, and mucinous ovarian cancer to FE. Reverse MR suggested all epilepsies increase lung cancer risk. eQTL analysis implicated iroquois homeobox 3 (IRX3), colony-stimulating factor 1 receptor (CSF1R), and Fibrillin-2 (FBN2) as shared genetic mechanisms, suggesting roles in metabolic reprogramming, inflammation, and extracellular matrix remodeling.