What is the clinical evidence from this study?

Study design: Observational. Population: Major depressive disorder, type 2 diabetes, coronary artery disease, heart failure. Intervention: Genetic liability to major depressive disorder. Primary outcome: Type 2 diabetes (OR 1.26, 95% CI 1.10, 1.43, p=6x10^-4).

April 8, 2020Open Access

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

Key Result

Genetic liability to major depressive disorder significantly increased the risk of type 2 diabetes (OR 1.26) and coronary artery disease (OR 1.16).

Study Design

Type

Observational

Structured PICO

Does genetic liability to major depressive disorder increase the risk of type 2 diabetes, coronary artery disease, and heart failure?

Population

Individuals mainly of European-descent from large genome-wide association studies

Intervention

Genetic liability to major depressive disorder (MDD) using 96 SNPs

Comparator

Reverse MR: Genetic liability to type 2 diabetes (202 SNPs), CAD (44 SNPs), and heart failure (12 SNPs)

Outcome

Type 2 diabetes, coronary artery disease, and heart failurehard clinical

This Mendelian randomisation study provides evidence that major depressive disorder is a potential causal risk factor for type 2 diabetes and coronary artery disease.

Main Result

Effect estimate: OR 1.26 (95% CI 1.10, 1.43)

p-value: p=6x10^-4

Limitations

Potential of pleiotropy.
BMI might be a pleiotropic factor or confounder in the pathway from MDD to type 2 diabetes.
Population stratification may have affected the result for the association between CAD and MDD because the GWAS of CAD included participants of different ancestry.

Abstract

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 log e 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 ).

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