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Title: | Evaluation of bi-directional causal association between depression and cardiovascular diseases: a Mendelian randomization study | Authors: | Li, GHY Cheung, CL Chung, AKK Cheung, BMY Wong, ICK Fok, MLY Au, PCM Sham, PC |
Issue Date: | Jul-2022 | Source: | Psychological medicine, July 2022, v. 52, no. 9, p. | 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. |
Keywords: | Cardiovascular disease Depression Genetics Mendelian randomization |
Publisher: | Cambridge University Press | Journal: | Psychological medicine | ISSN: | 0033-2917 | EISSN: | 1469-8978 | DOI: | 10.1017/S0033291720003566 | Rights: | This article has been published in a revised form in Psychological Medicine http://doi.org/10.1017/S0033291720003566. This version is free to view and download for private research and study only. Not for re-distribution or re-use. Copyright © The Author(s) 2020. Published by Cambridge University Press. When citing an Accepted Manuscript or an earlier version of an article, the Cambridge University Press requests that readers also cite the Version of Record with a DOI link. The article is subsequently published in revised form in Psychological Medicine https://dx.doi.org/10.1017/S0033291720003566. |
Appears in Collections: | Journal/Magazine Article |
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Depression_CVD_Manuscript_R2_submit_clean.pdf | Pre-Published version | 1.15 MB | Adobe PDF | View/Open |
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