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The Causal Effects of Psychiatric Disorders on Lung Cancer in Europeans: Bidirectional Mendelian-Randomization Analysis
33 Pages Posted: 7 Jul 2023
More...Abstract
Background & aimThe timely detection of risk factors is imperative in thwarting the progression of lung cancer in individuals with psychiatric disorders. However, the genetic foundation and causative association between psychiatric disorders and lung cancer remain ambiguous. Our objective was to methodically investigate the correlation between genetically anticipated psychiatric disorders and lung cancer.Methods This study employs genetic correlation and bidirectional two-sample generalized summary data-based mendelian randomization (GSMR) to investigate the genetic association between psychiatric disorders and lung cancer. The linkage disequilibrium score regression (LDSC) method was utilized to assess the genetic correlation. Additionally, bidirectional two-sample mendelian randomization analysis was conducted based on summary statistics data to further explore the causal relationship between these two traits. The causal association between psychiatric disorders and lung cancer was evaluated by using stochastic model inverse variance weighted (IVW), weighted median (WM) and maximum likelihood (ML) methods, and the consistency test of cardinal direction relations was performed using MR-egger method. To ensure the reliability of our results, we conducted sensitivity, heterogeneity analyses and selected a larger number of patients as a validation set to validate our conclusions. ResultsBased on extensive GWAS data, a strong positive genetic correlation (rg=0.36, P = 2.00×10-4) was found between psychiatric disorders and lung cancer. This correlation met the threshold for Bonferroni's correction. Bidirectional Mendelian randomization analysis indicated that a higher risk of psychiatric disorders was significantly associated with an increased risk of lung cancer. This finding was consistent across multiple sensitivity analyses and statistical models that controlled for confounding factors such as smoking and obesity. Furthermore, the data of a larger sample size of lung cancer in the IEU database was used as a validation set to verify the association between psychiatric disorders and lung cancer.ConclusionsOur study revealed a common genetic basis between psychiatric disorders and lung cancer, and identified that psychiatric disorders are genetically linked to a higher risk of lung cancer. The research provided a theoretical foundation for preventing the development of lung cancer in individuals with psychiatric disorders. Moreover, the findings emphasized the importance of identifying potential connections between psychiatric disorders and lung cancer, as well as elucidating underlying mechanisms.
Keywords: lung cancer, psychiatric disorders, genome-wide association study, prospective analysis, mendelian randomization, generalized summary data-based mendelian randomization
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