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

TY - JOUR

T1 - Evaluation of bi-directional causal association between depression and cardiovascular diseases

T2 - A Mendelian randomization study

AU - Li, Gloria Hoi Yee

AU - Cheung, Ching Lung

AU - Chung, Albert Kar Kin

AU - Cheung, Bernard Man Yung

AU - Wong, Ian Chi Kei

AU - Fok, Marcella Lei Yee

AU - Au, Philip Chun Ming

AU - Sham, Pak Chung

PY - 2020

Y1 - 2020

N2 - 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: 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. Results. Both 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. 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.

AB - 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: 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. Results. Both 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. 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.

KW - Cardiovascular disease

KW - Depression

KW - Genetics

KW - Mendelian randomization

UR - http://www.scopus.com/inward/record.url?scp=85093535747&partnerID=8YFLogxK

U2 - 10.1017/S0033291720003566

DO - 10.1017/S0033291720003566

M3 - Article

AN - SCOPUS:85093535747

SN - 0033-2917

JO - Psychological Medicine

JF - Psychological Medicine

ER -