Type 2 diabetes is causally associated with depression: a Mendelian randomization analysis

Abstract

Type 2 diabetes (T2D) has been associated with a high prevalence of depression. We aimed to determine the causal relation by performing a Mendelian randomization (MR) study using 34 T2D risk genetic variants validated in East Asians as the instrumental variable (IV). An MR analysis was performed involving 11 506 participants from a large longitudinal study. The T2D genetic risk score (GRS) was built using the 34 typical T2D common variants. We used T2D_GRS as the IV estimator and performed inverse-variance weighted (IVW) and Egger MR analysis. The T2D_GRS was found to be associated with depression with an OR of 1.21 (95% CI: 1.07–1.37) after adjustments for age, sex, body mass index, current smoking and drinking, physical activity, education, and marital status. Using T2D_GRS as the IV, we similarly found a causal relationship between genetically determined T2D and depression (OR: 1.84, 95% CI: 1.25–2.70). Though we found no association between the combined effect of the genetic IVs for T2D and depression with Egger MR (OR: 0.95, 95% CI: 0.42–2.14), we found an association for T2D and depression with IVW (OR: 1.75, 95% CI: 1.31–2.46) after excluding pleiotropic SNPs. Overall, the MR analyses provide evidence inferring a potential causal relationship between T2D and depression.

Keywords

causal modeling / depression / Mendelian randomization / type 2 diabetes

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Acknowledgements

Our study was supported by grants from the National Natural Science Foundation of China (Nos. 81471062, 81471059, 81500660, and 81561128019), the Ministry of Science and Technology of China (Nos. 2016YFC1305600, 2016YFC1304904, and 2018YFC1311705), the National International Science Cooperation Foundation (No. 2015DFA30560), and the Gaofeng Clinical Medicine Grant Support of the Shanghai Municipal Education Commission (Nos. 20152508 and 20161301).

Compliance with ethics guidelines

Liping Xuan, Zhiyun Zhao, Xu Jia, Yanan Hou, Tiange Wang, Mian Li, Jieli Lu, Yu Xu, Yuhong Chen, Lu Qi, Weiqing Wang, Yufang Bi, and Min Xu declare that they have no conflicts of interest. The study protocol was approved by the Institutional Review Board of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Informed consent was obtained from all individual participants included in this study.

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