Causal link between mental diseases and gastrointestinal diseases based on a Mendelian randomization study

Wenjing Ding ¹ Liangliang Chen ² Bei Pei ¹ Yougang Wang ² Dahong Gao ² Jianguo Xia ² Xuejun Li ^2*

• ¹ The Second Clinical Medical School, Anhui University of Chinese Medicine, Hefei, China
• ² Department of Gastroenterology, The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China

Background: Observational researches have suggested that mental diseases may cause the risk of gastrointestinal diseases. However, the causal link between mental diseases and gastrointestinal diseases still remains unclear. In this paper, we utilized a two-sample Mendelian randomization study to assess the causal relationships between common mental diseases and the risk of gastrointestinal diseases. Methods: Firstly, a series of parameters were set to obtain the single-nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS). Secondly, two-sample Mendelian randomization was used to analyze the causal link between mental diseases (Alzheimer's disease, depression, major depressive disorder, Parkinson's disease, schizophrenia) and gastrointestinal diseases (gastritis and duodenitis, gastric cancer) with getting rid of outliers based on MR-PRESSO. Finally, eight methods of MR analysis were employed to display forest plots, including inverse variance weighted (IVW), inverse variance weighted (fixed effects) (IVW fixed effects), maximum likelihood (ML), MR Egger, weighted median, penalised weighted median, simple mode, weighted mode, which IVW was considered as the main method. Results: The result demonstrated that most of MDs have no evidence of a causal link between gastrointestinal diseases except Parkinson's disease and gastric cancer based on IVW method [OR: 0.929, 95% CI: 0.869-0.992, p = 0.029]. Then, we conducted a consistent robustness analysis. Conclusions: Our method found the evidence to support the causal link between Parkinson's disease and the risk of gastric cancer, but other mental diseases had no evidence to cause the risk of gastrointestinal diseases. Further researches are still warrented to discover how mental diseases have influence on the development of gastrointestinal diseases.