Genetic Liability to Depression and Risk of Coronary Artery Disease, Myocardial Infarction, and Other Cardiovascular Outcomes

Abstract

Background Observational studies have indicated that depression is associated with coronary artery disease (CAD) and myocardial infarction. Nevertheless, causal associations between depression and cardiovascular diseases remain controversial. Hence, we conducted a Mendelian randomization and mediation analysis to evaluate the associations of depression‐related genetic variants with CAD and myocardial infarction. Methods and Results Summary statistics from genome‐wide association studies of depression (807 553 individuals), and CAD (60 801 cases, including 43 676 with myocardial infarction, and 123 504 controls) were used. We pooled Mendelian randomization estimates using a fixed‐effects inverse‐variance weighted meta‐analysis and multivariable Mendelian randomization. The mediation effects of potential cardiovascular risk factors on depression‐CAD and myocardial infarction risk were investigated by using mediation analysis. We also explored the relationship of genetic liability to depression with heart failure, atrial fibrillation, and ischemic stroke. Genetic liability to depression was associated with higher CAD (odds ratio [OR], 1.14; 95% CI, 1.06–1.24; P =1.0×10 −3 ) and myocardial infarction (OR, 1.21; 95% CI, 1.11–1.33; P =4.8×10 −5 ) risks. Results were consistent in all sensitivity analyses. Type 2 diabetes mellitus and smoking demonstrated significant mediation effects. Furthermore, our Mendelian randomization analyses revealed that the genetic liability to depression was associated with higher risks of heart failure and small vessel stroke. Conclusions Genetic liability to depression is associated with higher CAD and myocardial infarction risks, partly mediated by type 2 diabetes mellitus and smoking. The potential preventive value of depression treatment on cardiovascular diseases should be investigated in the future.

Association of Autism Spectrum Disorder, Neuroticism, and Subjective Well-Being With Cardiovascular Diseases: A Two-Sample Mendelian Randomization Study

“…Recently, this method has been used to estimate the causal relationship between depression and the risk of CVDs. Li et al demonstrated that depression was causally associated with a higher risk of CAD [odds ratio (OR), 1.099; 95% CI, 1.031-1.170; P = 0.004] and MI (OR, 1.146; 95% CI, 1.070-1.228; P = 1.05 × 10 −4 ) (11), which was consistent with other two MR studies (12,13). However, there is limited or no MR study when it comes to other psychiatric traits.…”

Shared genetic loci between depression and cardiometabolic traits

“…While twin studies have found bidirectional associations between depression and CAD [ 23 , 24 ], the specific genes linking depression and CAD are not known and the cause of this association remain unclear (1). Mendelian randomization has indicated that the genetic liability to depression is associated with higher CAD and myocardial infarction risks, partly mediated by type 2 diabetes mellitus and smoking [ 43 ]. Furthermore, an increase in polygenic score for depression was associated with CAD [ 44 ].…”

Association of mental health with the risk of coronary artery disease in patients with diabetes: A mendelian randomization study

“…The genetic responsibility of depression is associated with CAD risk factors such as endothelial dysfunction [37], hypertension [38], and obesity [39]. A recent MR analysis found a causal association between depression and CAD in the general population [18]. Our MR analysis using the summarized GWAS dataset yielded genetic evidence of the causality between depression and CAD in patients with diabetes.…”

“…Recently, a two-sample MR study suggested depression was associated with increased CAD risk. [18], and another MR study showed that neuroticism was casually associated with a higher risk of atrial fibrillation [19]. However, no MR studies have explored the causality between mental health and CAD in patients with diabetes.…”