Genetically predicted mood disorders increased risk of cisplatin-induced hearing loss in childhood cancer: Evidence from a bidirectional Mendelian randomization study

Children with cancer often suffer from hearing loss caused by cisplatin, which is often accompanied by more frequent mood swings. However, the causal relationship between the 2 remains unclear. This study investigated whether mood swings have a causal effect on cisplatin-induced hearing loss in childhood cancer. We obtained genome-wide association data for mood swings and cisplatin-induced hearing loss in childhood cancer from the Mendelian randomization (MR) base platform. Significant single nucleotide polymorphisms associated with mood swings were used as instrumental variables in 2-sample MR analyses. The causal relationship was examined using the inverse-variance weighted method, weighted median estimator, and MR-Egger regression. A total of 40 single nucleotide polymorphisms significantly linked to mood swings (P < 5 × 10-8; linkage disequilibrium r2 < 0.001) were identified. All methods consistently indicated a positive association between mood swings and cisplatin-induced hearing loss (inverse-variance weighted: odds ratio [OR]: 445.531, 95% confidence interval [CI]: 14.667-13533.950; weighted median: OR: 203.819, 95% CI: 2.113-19663.482; MR-Egger: OR: 100.431, 95% CI: 10-7 to 1010). In contrast, no causal effect was found for genetic predisposition to cisplatin-induced hearing loss on mood swings. The findings provide strong evidence that frequent mood swings may causally increase the risk of cisplatin-induced hearing loss in childhood cancer.