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. 2020 Jul;63(7):1305-1311.
doi: 10.1007/s00125-020-05131-6. Epub 2020 Apr 8.

Major depressive disorder and cardiometabolic diseases: a bidirectional Mendelian randomisation study

Bowen Tang  1 , Shuai Yuan  1   2   3 , Ying Xiong  1 , Qiqiang He  4 , Susanna C Larsson  5   6
Affiliations

Major depressive disorder and cardiometabolic diseases: a bidirectional Mendelian randomisation study

Bowen Tang et al. Diabetologia. 2020 Jul.

Abstract

Aims/hypothesis: Observational studies have shown a bidirectional association between major depressive disorder (MDD) and cardiometabolic diseases. We conducted a two-sample bidirectional Mendelian randomisation (MR) study to assess the causal associations of MDD with type 2 diabetes, coronary artery disease (CAD) and heart failure and vice versa.

Methods: We extracted summary-level data for MDD, type 2 diabetes, CAD and heart failure from corresponding published large genome-wide association studies of individuals mainly of European-descent. In total, 96 SNPs for MDD, 202 SNPs for type 2 diabetes, 44 SNPs for CAD and 12 SNPs for heart failure were proposed as instrumental variables at the genome-wide significance level (p < 5 × 10-8). The random-effects inverse-variance weighted method was used for the main analyses.

Results: Genetic liability to MDD was significantly associated with type 2 diabetes and CAD at the Bonferroni-corrected significance level. The ORs of type 2 diabetes and CAD were respectively 1.26 (95% CI 1.10, 1.43; p = 6 × 10-4) and 1.16 (95% CI 1.05, 1.29; p = 0.0047) per one-unit increase in loge odds of MDD. There was a suggestive association between MDD and heart failure (OR 1.11 [95% CI 1.01, 1.21]; p = 0.033). We found limited evidence supporting causal effects of cardiometabolic diseases on MDD risk in the reverse MR analyses.

Conclusions/interpretation: The present study strengthened the evidence that MDD is a potential risk factor for type 2 diabetes and CAD. Whether MDD is causally related to heart failure needs further study.

Data availability: All data included in this study were uploaded as supplements and are also publicly available through published GWASs and open GWAS datasets (UK Biobank, 23andMe and Psychiatric Genomics: https://datashare.is.ed.ac.uk/handle/10283/3203; DIAGRAM: http://diagram-consortium.org/downloads.html; CARDIoGRAMplusCD4: www.cardiogramplusc4d.org/; HERMES: http://www.kp4cd.org/datasets/mi). Graphical abstract.

Keywords: Coronary artery disease; Heart failure; Major depression disorder; Mendelian randomisation analysis; Type 2 diabetes.

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Figures

None
Graphical abstract
Fig. 1
Fig. 1
Assumptions and study design of the present bidirectional MR study of the associations of MDD with type 2 diabetes, CAD and heart failure. Grey lines show the relationship across instrumental variables, exposure, and outcomes in the MR study examining the effects of MDD on cardiometabolic diseases, and red lines show these relationships in the reverse MR study. Solid lines represent relationship that were observed, whereas dashed lines represent associations that would violate the MR assumptions (i.e. relationships that are not allowed/did not exist in the present MR study). Blue ticks indicate that genetic variants are associated with the exposure/outcome; red crosses indicate that genetic variants are not associated with any confounders of the exposure–outcome association; purple crosses indicate that genetic variants exert effects on the outcome only via the exposure. HF, heart failure; T2DM, type 2 diabetes
Fig. 2
Fig. 2
Associations of genetic liability to MDD with risk of type 2 diabetes, CAD and heart failure
Fig. 3
Fig. 3
Associations of genetic liability to type 2 diabetes, CAD and heart failure with MDD
See this image and copyright information in PMC

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