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

Gloria Hoi-Yee Li; Ching-Lung Cheung; Albert Kar-Kin Chung; Bernard Man-Yung Cheung; Ian Chi-Kei Wong; Marcella Lei Yee Fok; Philip Chun-Ming Au; Pak-Chung Sham

doi:10.1017/S0033291720003566

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

Psychol Med. 2022 Jul;52(9):1765-1776. doi: 10.1017/S0033291720003566. Epub 2020 Oct 9.

Authors

Affiliations

¹ Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
² Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong.
³ Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
⁴ Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
⁵ Research Department of Practice and Policy, School of Pharmacy, University College London, London, UK.
⁶ Central and North West London NHS Foundation Trust, London, UK.
⁷ Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁸ State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong.

PMID: 33032663
DOI: 10.1017/S0033291720003566

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: r_G = 0.169; p = 9.03 × 10^-9; broad depression: r_G = 0.123; p = 1 × 10^-4) and AF (depression: r_G = 0.112; p = 7.80 × 10^-6; broad depression: r_G = 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.

Keywords: Cardiovascular disease; Mendelian randomization; depression; genetics.

Publication types

Meta-Analysis

MeSH terms

Cardiovascular Diseases* / epidemiology
Cardiovascular Diseases* / genetics
Coronary Artery Disease
Depression / epidemiology
Depression / genetics
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Myocardial Infarction
Polymorphism, Single Nucleotide
Risk Factors
Stroke* / epidemiology
Stroke* / genetics

Supplementary concepts

Coronary Artery Disease, Autosomal Dominant, 1