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. 2024 Feb 16:14:1321445.
doi: 10.3389/fonc.2024.1321445. eCollection 2024.

Genetic prediction of the causal relationship between schizophrenia and tumors: a Mendelian randomized study

Xintong Zhou #  1 , Qi Liu #  1 , Shihan Liu  2 , Liquan Wang  3 , Zhongli Sun  1 , Changgang Sun  4   5 , Xiangning Cui  6
Affiliations

Genetic prediction of the causal relationship between schizophrenia and tumors: a Mendelian randomized study

Xintong Zhou et al. Front Oncol. .

Abstract

Background: Patients with schizophrenia are at a higher risk of developing cancer. However, the causal relationship between schizophrenia and different tumor types remains unclear.

Methods: Using a two-sample, two-way Mendelian randomization method, we used publicly available genome-wide association analysis (GWAS) aggregate data to study the causal relationship between schizophrenia and different cancer risk factors. These tumors included lung adenocarcinoma, lung squamous cell carcinoma, small-cell lung cancer, gastric cancer, alcohol-related hepatocellular cancer, tumors involving the lungs, breast, thyroid gland, pancreas, prostate, ovaries and cervix, endometrium, colon and colorectum, and bladder. We used the inverse variance weighting (IVW) method to determine the causal relationship between schizophrenia and different tumor risk factors. In addition, we conducted a sensitivity test to evaluate the effectiveness of the causality.

Results: After adjusting for heterogeneity, evidence of a causal relationship between schizophrenia and lung cancer risk was observed (odds ratio [OR]=1.001, 95% confidence interval [CI], 1.000-1.001; P=0.0155). In the sensitivity analysis, the causal effect of schizophrenia on the risk of lung cancer was consistent in both direction and degree. However, no evidence of causality or reverse causality between schizophrenia and other tumors was found.

Conclusion: This study elucidated a causal relationship between the genetic predictors of schizophrenia and the risk of lung cancer, thereby providing a basis for the prevention, pathogenesis, and treatment of schizophrenia in patients with lung cancer.

Keywords: GWAS; cancer; causality; mendelian randomization; schizophrenia.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Two-sample Mendelian randomized study design for schizophrenia and different cancers. Solid blue lines indicate the association between tool variables (SNP) and exposure (schizophrenia) and between exposure and outcome (different types of tumors). The red solid line indicates the correlation of reverse causality. The dotted line with crossover indicates that this association conforms to two basic assumptions of Mendelian randomization: 1. Genetic variation (SNP) is independent of the confounding factor between exposure and outcome 2. Genetic variation affects the results only through exposure.
Figure 2
Figure 2
MR Scatter plot.
Figure 3
Figure 3
MR leave-one-out sensitivity analysis for Schizophrenia on Lung cancer.
See this image and copyright information in PMC

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