Mendelian randomization shows depression increases the risk of type 2 diabetes

Heejin Jin; Sanghun Lee; Sungho Won

doi:10.3389/fgene.2023.1181851

Mendelian randomization shows depression increases the risk of type 2 diabetes

Front Genet. 2023 Aug 24:14:1181851. doi: 10.3389/fgene.2023.1181851. eCollection 2023.

Authors

Heejin Jin¹, Sanghun Lee², Sungho Won³

Affiliations

¹ Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea.
² Department of Medical Consilience, Graduate School, Dankook University, Yongin-si, Republic of Korea.
³ Department of Public Health Science, Seoul National University and Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea.

Abstract

Introduction: Type 2 diabetes (T2D) is associated with severe mental illnesses (SMIs), such as schizophrenia, bipolar disorder, and depression. However, causal relationships between SMIs and T2D remain unclear owing to potential bias in observational studies. We aimed to characterize the causal effect of SMI liability on T2D using two-sample Mendelian randomization (MR). Methods: The causality between liability to SMI and T2D was investigated using the inverse-variance weighted (IVW), MREgger, MR-Egger with a simulation extrapolation, weighted median, and the MR pleiotropy residual sum and outlier method. Similarly, we performed additional MR which can detect the reverse causation effect by switching exposure and outcome for T2D liability for SMI. To further consider pleiotropic effects between SMIs, multivariable MR analysis was performed after accounting for the other traits. Results: In the univariable IVW method, depression showed a causal effect on T2D (odds ratio [OR]: 1.128, 95% confidence interval [CI]: 1.024-1.245, p = 0.014). Multinomial MR more strongly supported these results (IVW OR: 1.197, 95% CI: 1.069, 1.340, p = 0.002; MR-Egger OR: 1.198, 95% CI: 1.062, 1.349, p = 0.003). Bidirectional MR showed absence of reversecausality between depression and T2D. However, causal relationship of bipolar and schizophrenia on T2D was not detected. Discussion: Careful attention is needed for patients with depression regarding T2D prevention and treatment.

Keywords: bipolar disorder; causality; depression; mendelian randomization analysis; schizophrenia; type 2 diabetes mellitus.

Grants and funding

Statistical analyses were supported by the national supercomputing center with supercomputing resources including technical support (KSC-2022-CRE-0319) and data was provided with bioresources from National Biobank of Korea, the Korea Disease Control and Prevention Agency, Republic of Korea (NBK-2020-101). This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI22C0154); and the National Research Foundation (NRF) grant (NRF-2021R1A5A1033157) funded by the Korean government (MSIT).