ArticleEClinicalMedicine2025
Genetic susceptibility to depression and risk of cardiometabolic diseases: a systematic review and meta-analysis of 21 Mendelian randomisation studies.
Article in EClinicalMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A review of the relationship between dimensions of alcohol consumption and the burden of disease: 2026 update including Mendelian randomisation studies.Addiction (Abingdon, England) · 2026Pooled it
- The emerging potential of the psycho-cardiovascular interaction network in precision medicine.Precision clinical medicine · 2026Article
- Joint effects of depression, lipid metabolic dysfunction, and their trajectories on incident cardiometabolic multimorbidity: a prospective multi-cohort analysis from two national cohorts.Lipids in health and disease · 2026Article
- Deciphering the potential molecular network underlying nicotine- and its metabolite cotinine-induced myocardial infarction via network toxicology, molecular dynamics, and in vitro experimental validation.Functional & integrative genomics · 2026Article
Corrections and comments
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Depression is a risk factor for cardiometabolic diseases, but the extent to which this is attributable to genetic (rather than environmental) factors is unclear. Mendelian randomisation (MR) uses genetic variants to infer causality. We aimed to investigate the bidirectional association between respective genetic susceptibility to depression and cardiometabolic diseases. Methods: We conducted a systematic review and meta-analysis of MR studies (unidirectional or bidirectional) in adults that assessed associations between genetic variants related to depression and any cardiometabolic disease. A comprehensive literature search of MEDLINE, EMBASE, PsycINFO, CINAHL, Scopus, Web of Science, and Cochrane Library was performed to capture relevant articles published between database inception to June 20, 2024. This search was updated on April 23, 2025. Reference lists of included articles were manually searched for additional records. Articles published in English or translated into English were included. Primary outcomes of interest included cardiovascular diseases (six) and metabolic diseases (three). Contextually similar studies were pooled and sub-grouped based on population ancestry, study design, and outcome definition. A customised risk of bias tools for Mendelian randomisation was used to assess the risk of bias across five domains. Heterogeneity was assessed via I2 and tau-squared (τ2) statistics and publication bias was assessed via visual inspection of contour-enhanced funnel plots. This work is registered with PROSPERO, CRD42023460334. Findings: We included 79 studies (294 MR analyses) in the systematic review and 21 studies (29 MR analyses) in the meta-analysis. For the primary outcomes eligible for pooling, genetic susceptibility to depression was associated with increased odds of coronary artery disease (odds ratio 1.12, 95% CI 1.05-1.19; k = 3, Interpretation: Our findings suggest that depression and cardiometabolic diseases are associated with each other. Though the observed effects are small and of limited immediate clinical relevance, our findings reflect the genetic component of the association separately to the behavioural and environmental influences. Treatment strategies identifying those at risk could benefit both diseases; however, high heterogeneity warrants cautious interpretation of our findings. Funding: None.
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