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

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). [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-020-05131-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users.