Evaluation of bi-directional causal association between depression and cardiovascular diseases: a Mendelian randomization study.

Background: Depression and cardiovascular disease (CVD) are associated with each other but their relationship remains unclear. We aim to determine whether genetic predisposition to depression are causally linked to CVD [including coronary artery disease (CAD), myocardial infarction (MI), stroke and atrial fibrillation (AF)].

Methods: Using summary statistics from the largest genome-wide association studies (GWAS) or GWAS meta-analysis of depression (primary analysis: = 500 199), broad depression (help-seeking behavior for problems with nerves, anxiety, tension or depression; secondary analysis: = 322 580), CAD ( = 184 305), MI ( = 171 875), stroke ( = 446 696) and AF ( = 1 030 836), genetic correlation was tested between two depression phenotypes and CVD [MI, stroke and AF (not CAD as its correlation was previously confirmed)]. Causality was inferred between correlated traits by Mendelian Randomization analyses.

Results: Both depression phenotypes were genetically correlated with MI (depression: = 0.169; = 9.03 × 10; broad depression: = 0.123; = 1 × 10) and AF (depression: = 0.112; = 7.80 × 10; broad depression: = 0.126; = 3.62 × 10). Genetically doubling the odds of depression was causally associated with increased risk of CAD (OR = 1.099; 95% CI 1.031-1.170; = 0.004) and MI (OR = 1.146; 95% CI 1.070-1.228; = 1.05 × 10). Adjustment for blood lipid levels/smoking status attenuated the causality between depression and CAD/MI. Null causal association was observed for CVD on depression. A similar pattern of results was observed in the secondary analysis for broad depression.

Conclusions: Genetic predisposition to depression may have positive causal roles on CAD/MI. Genetic susceptibility to self-awareness of mood problems may be a strong causal risk factor of CAD/MI. Blood lipid levels and smoking may potentially mediate the causal pathway. Prevention and early diagnosis of depression are important in the management of CAD/MI.