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

• Published in: Psychological medicine 2022-07, Vol.52 (9), p.1765-1776
• Main Authors: Li, Gloria Hoi-Yee, Cheung, Ching-Lung, Chung, Albert Kar-Kin, Cheung, Bernard Man-Yung, Wong, Ian Chi-Kei, Fok, Marcella Lei Yee, Au, Philip Chun-Ming, Sham, Pak-Chung
• Format: Article
• Language: English
• Subjects: Analysis; Atrial fibrillation; Biobanks; Blood; Cardiovascular disease; Cardiovascular diseases; Causality; Cerebral infarction; Coronary artery; Coronary artery disease; Datasets; Fibrillation; Genetic analysis; Genetic susceptibility; Genome-wide association studies; Genomes; Genomics; Heart diseases; Help seeking behavior; Medical diagnosis; Mental depression; Meta-analysis; Myocardial infarction; Nerves; Original Article; Phenotypes; Risk factors; Sample size; Selfawareness; Smoking; Statistical analysis; Susceptibility
• ISSN: 0033-2917; 1469-8978
• DOI: 10.1017/S0033291720003566

BackgroundDepression 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.