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. 2018 Dec;12(6):678-687.
doi: 10.1007/s11684-018-0671-7. Epub 2018 Nov 16.

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

Liping Xuan  1   2   3 , Zhiyun Zhao  1   2   3 , Xu Jia  1   2   3 , Yanan Hou  1   2   3 , Tiange Wang  1   2   3 , Mian Li  1   2   3 , Jieli Lu  1   2   3 , Yu Xu  1   2   3 , Yuhong Chen  1   2   3 , Lu Qi  4 , Weiqing Wang  1   2   3 , Yufang Bi  1   2   3 , Min Xu  5   6   7
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Type 2 diabetes is causally associated with depression: a Mendelian randomization analysis

Liping Xuan et al. Front Med. 2018 Dec.

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 EggerMR(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: Mendelian randomization; causal modeling; depression; type 2 diabetes.

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