Noncausal effects of genetic predicted depression and gastric cancer risk: A NHANES and Mendelian randomization study

Abstract

The relationship between gastric cancer and depression remains an area of active investigation, with recent studies suggesting a potential bidirectional association. We present an analysis of the correlation between gastric cancer and depression using data from the National Health and Nutrition Examination Survey (NHANES) and Genome-Wide Association Studies (GWAS), employing Mendelian Randomization (MR) to explore the causal links between these conditions. The NHANES analysis adjusted for confounders such as lifestyle factors and pre-existing health conditions, revealing a higher incidence of depression among individuals with gastric cancer. Stepwise regression models further established depression as a risk factor for developing gastric cancer. Conversely, MR analysis using genetic variants as instrumental variables suggested that gastric cancer significantly impacts the development of depression, with 24 single nucleotide polymorphisms (SNPs) showing a significant association with both conditions. The Inverse Variance Weighted (IVW) method indicated a significant effect of gastric cancer on depression (OR: 0.979[0.962-0.995]), although the strength of the association varied with different weighting methods. Reverse MR analysis did not find a significant impact of depression on the occurrence of gastric cancer, with 15 SNPs associated with both diseases but no significant effect observed (OR: 0.834 [0.504-1.380]). The study's findings underscore the importance of considering mental well-being in the treatment of gastric cancer and provide a new direction for future therapeutic approaches. However, limitations such as the focus on individuals of European ancestry and the lack of specificity regarding types of gastric cancer warrant further research.