Abstract
AbstractBackgroundDepression 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)].MethodsUsing summary statistics from the largest genome-wide association studies (GWAS) or GWAS meta-analysis of depression (primary analysis:n= 500 199), broad depression (help-seeking behavior for problems with nerves, anxiety, tension or depression; secondary analysis:n= 322 580), CAD (n= 184 305), MI (n= 171 875), stroke (n= 446 696) and AF (n= 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.ResultsBoth depression phenotypes were genetically correlated with MI (depression:rG= 0.169;p= 9.03 × 10−9; broad depression:rG= 0.123;p= 1 × 10−4) and AF (depression:rG= 0.112;p= 7.80 × 10−6; broad depression:rG= 0.126;p= 3.62 × 10−6). Genetically doubling the odds of depression was causally associated with increased risk of CAD (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). 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.ConclusionsGenetic 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.
Publisher
Cambridge University Press (CUP)
Subject
Psychiatry and Mental health,Applied Psychology
Cited by
36 articles.
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