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

Published online by Cambridge University Press:  09 October 2020

Gloria Hoi-Yee Li
Affiliation:
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong
Ching-Lung Cheung
Affiliation:
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
Albert Kar-Kin Chung
Affiliation:
Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
Bernard Man-Yung Cheung
Affiliation:
Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
Ian Chi-Kei Wong
Affiliation:
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Research Department of Practice and Policy, School of Pharmacy, University College London, London, UK
Marcella Lei Yee Fok
Affiliation:
Central and North West London NHS Foundation Trust, London, UK Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
Philip Chun-Ming Au
Affiliation:
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
Pak-Chung Sham
Affiliation:
Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong
Corresponding
E-mail address:

Abstract

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.

Type
Original Articles
Copyright
Copyright © The Author(s) 2020. Published by Cambridge University Press

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