Psychiatric disorders and Type 2 diabetes mellitus: A bidirectional Mendelian randomization

Abstract

Background: Extensive observational evidence put forward the association between psychiatric disorders and type 2 diabetes mellitus (T2DM). However, causal relationships between these two diseases required further research. Thus, we evaluated the bidirection casual effect between five psychiatric disorders and T2DM using two-sample mendelian randomization (MR).

Methods: By selecting single nucleotide polymorphisms associated with T2DM and five psychiatric disorders (attention-deficit hyperactivity disorder (ADHD), major depressive disorder (MDD), schizophrenia, anxiety disorder and panic disorder), a bidirectional two-sample MR was applied to evaluate causality between these diseases. The inverse-variance weighted (IVW) method was used as the primary analysing approach for estimating possible causal effects. MR-Egger and weighted median were also conducted to verify the results. The funnel plot, Cochran's Q test and MR-Egger intercept test were used for sensitivity analyses. In addition, potential mediators were investigated by risk factor analyses.

Results: Genetic susceptibilities of ADHD and MDD would increase the risk of T2DM (ADHD: OR = 1.14, 95%CI 1.08-1.20; $p=5.7\times {10}^{-6}$ ; MDD: OR = 1.22, 95%CI 1.09-1.36; $p=0.0004$ ). In addition, genetic predisposition to T2DM was also associated with ADHD (OR = 1.09, 95%CI 1.04-1.14; p = 0.0004). Several risk factors of T2DM were implicated in the above causal associations, including smoking, high body mass index, waist-to-hip ratio and elevated serum triglycerides.

Conclusion: Our studies indicated a causal effect of ADHD and MDD on increasing the risk of T2DM, which was potentially mediated by smoking and obesity-related phenotypes. Meanwhile, we found a causal effect of T2DM on ADHD. Thus, prevention strategies for T2DM should also include mental health and vice versa.

Keywords: attention-deficit hyperactivity disorder; diabetes; mendelian randomization; psychiatric disorders.