Psychiatric Traits and Risk of Mouth Ulcers: A Two-Sample Bi-Directional Mendelian Randomization Study

Abstract

Background: The association between mouth ulcers and psychiatric traits has been reported by observational studies. However, their causal relationship remains unclear. Methods: We collected summary statistics of mouth ulcers and ten psychiatric traits from the largest publicly available genome-wide association studies (GWAS) on Europeans, including anxiety disorder (sample size n=83,566), attention deficit/hyperactivity disorder (n=53,293), autism spectrum disorder (n=46,350), bipolar disorder (n=51,710), insomnia (n=1,331,010), major depressive disorder (n=480,359), mood instability (n=363,705), neuroticism (n=168,105), schizophrenia (n=105,318), and subjective well-being (n=388,538). For each psychiatric trait, we conducted two-sample bi-directional Mendelian randomization (MR) analyses to assess its causal relationship with mouth ulcers. Findings: We found strong evidence that autism spectrum disorder, insomnia, major depressive disorder, mood instability, and subjective well-being had causal effects on mouth ulcers, and the corresponding odds ratio (OR) (95% CI ) were 1.160 (95% CI : 1.066-1.261, P=5.39×10-4), 1.092 (1.062-1.122, P=3.37×10-10), 1.234 (1.134-1.342, P=1.03×10-6), 1.662 (1.059-2.609, P=0.027), and 0.703 (0.571-0.865, P=8.97×10-4), respectively. These results were robust to weak instrument bias and heterogeneity. We found no evidence on causal effects between other psychiatric traits and mouth ulcers, in either direction. Interpretation: Our findings suggest a protective effect of subjective well-being, and risk effects of autism spectrum disorder, insomnia, major depressive disorder, and mood instability on mouth ulcers. Our results clarify the causal relationship between psychiatric traits and the development of mouth ulcers. Funding Statement: This study was supported by the Natural Science Foundation of China (NSFC 81973148) and the Huazhong University of Science and Technology. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Because this study used published GWAS summary statistics available in the public domain, specific ethical review or consent from study participants was not sought.