Shared Genetic Liability and Causal Associations Between Major Depressive Disorder and Cardiovascular Diseases

Zhang, Fuquan; Cao, Hongbao; Baranova, Ancha

doi:10.3389/fcvm.2021.735136

Cited by 28 publications

(30 citation statements)

References 78 publications

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“…Mendelian randomization (MR) is an analytic framework that utilizes genetic variants as instrumental variables to test the causative association between an exposure and an outcome ( 19 ), which has been widely used in recent studies ( 20 – 22 ). In particular, previous MR analyses have reported causal risk factors for a severe course of COVID-19, including body mass index and smoking intensity ( 23 – 25 ).…”

Section: Introductionmentioning

confidence: 99%

Causal Association and Shared Genetics Between Asthma and COVID-19

et al. 2022

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ObjectivesRecent studies suggest that asthma may have a protective effect on COVID-19.We aimed to investigate the causality between asthma and two COVID-19 outcomes and explore the mechanisms underlining this connection.MethodsSummary results of GWAS were used for the analyses, including asthma (88,486 cases and 447,859 controls), COVID-19 hospitalization (6,406 hospitalized COVID-19 cases and 902,088 controls), and COVID-19 infection (14,134 COVID-19 cases and 1,284,876 controls). The Mendelian randomization (MR) analysis was performed to evaluate the causal effects of asthma on the two COVID-19 outcomes. A cross-trait meta-analysis was conducted to analyze genetic variants within two loci shared by COVID-19 hospitalization and asthma.ResultsAsthma is associated with decreased risk both for COVID-19 hospitalization (odds ratio (OR): 0.70, 95% confidence interval (CI): 0.70-0.99) and for COVID-19 infection (OR: 0.83, 95%CI: 0.51-0.95). Asthma and COVID-19 share two genome-wide significant genes, including ABO at the 9q34.2 region and OAS2 at the 12q24.13 region. The meta-analysis revealed that ABO and ATXN2 contain variants with pleiotropic effects on both COVID-19 and asthma.ConclusionIn conclusion, our results suggest that genetic liability to asthma is associated with decreased susceptibility to SARS-CoV-2 and to severe COVID-19 disease, which may be due to the protective effects of ongoing inflammation and, possibly, related compensatory responses against COVID-19 in its early stage.

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Section: Introductionmentioning

confidence: 99%

Causal Association and Shared Genetics Between Asthma and COVID-19

et al. 2022

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“…Third, though handgrip strength is an objective and common marker of muscular strength, it mainly represents upper body strength. Fourth, as the causal association was evaluated using MR based on the genetic information of each trait, the result should be interpreted with caution ( 42 ), with the understanding that the development of handgrip strength and CVDs were multifactorial and involved interactions among plenty of psycho-social-environmental factors ( 43 ). Finally, some samples in the GWAS of AF and HF have also been included in the UK Biobank, which may introduce bias.…”

Section: Discussionmentioning

confidence: 99%

Assessment of causal associations between handgrip strength and cardiovascular diseases: A two sample mendelian randomization study

Zhuo

Zhao²,

Wang³

et al. 2022

Front. Cardiovasc. Med.

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BackgroundSeveral observational studies have identified that handgrip strength was inversely associated with cardiovascular diseases (CVDs). Nevertheless, causality remains controversial. We conducted Mendelian randomization (MR) analysis to examine whether handgrip strength and risk of CVDs are causally associated.MethodsWe identified 160 independent single nucleotide polymorphisms (SNPs) for right-hand grip strength and 136 independent SNPs for left-hand grip strength at the genome-wide significant threshold (P < 5 × 10−8) from UK Biobank participants and evaluated these in relation to risk of CVDs. MR estimates was calculated using the inverse-variance weighted (IVW) method and multiple sensitivity analysis was further conducted.ResultsGenetical liability to handgrip strength was significantly associated with coronary artery disease (CAD) and myocardial infarction (MI), but not stroke, hypertension, or heart failure. Additionally, there was significant association between right-hand grip strength and atrial fibrillation (OR, 0.967; 95% CI, 0.950–0.984; p = 0.000222), however, suggestive significance was found between left-hand grip strength and atrial fibrillation (OR, 0.977; 95% CI, 0.957–0.998; p = 0.033). Results were similar in several sensitivity analysis.ConclusionOur study provides support at the genetic level that handgrip strength is negatively associated with the risk of CAD, MI, and atrial fibrillation. Specific handgrip strength interventions on CVDs warrant exploration as potential CVDs prevention measures.

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“…First, although we have excluded potential pleiotropic SNPs and MR-Egger regression indicated little horizontal pleiotropy, the influence of pleiotropy bias remains a concern in this study. Specifically, psychiatric traits such as major depressive disorder and neuroticism may be confounding factors in the causal associations between asthma and CVDs ( Cao et al, 2021 ; Wu et al, 2021 ; Zhang et al, 2021 , 2022 ). Besides, the divergent results of sensitivity analyses may indicate a bias of genetic pleiotropy towards asthma-AF and asthma-HF associations that we observed.…”

Section: Discussionmentioning

confidence: 99%

Genetic liability to asthma and risk of cardiovascular diseases: A Mendelian randomization study

Chen

Zheng

2022

Front. Genet.

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Background and Aims: Epidemiological studies have suggested positive associations between asthma and the risk of cardiovascular diseases (CVDs). However, causality remains inconclusive. We aim to explore the causal associations between asthma and CVDs risk using the Mendelian Randomization (MR) approach.Methods: We obtained summary-level data for eight CVDs [including atrial fibrillation (AF), coronary artery disease (CAD), heart failure (HF), stroke, ischemic stroke, large artery stroke, small vessel stroke, and cardioembolic stroke] from several large genome-wide association studies (GWASs) and the FinnGen consortium. Nine lead single-nucleotide polymorphisms associated with asthma (p < 5 × 10−8) were identified from the GWAS conducted by the Trans-National Asthma Genetic Consortium. MR analyses were performed using the inverse variance weighted method, supplemented by the weighted median and MR-Egger methods.Results: Inverse variance weighted method showed suggestive effects of genetically determined asthma on AF (odds ratio (OR), 1.08; 95% confidence interval (CI), 1.02, 1.14; p = 0.009) and HF (OR, 1.05; 95% CI, 1.01, 1.09; p = 0.029). We found no causal associations between asthma and other CVDs. No horizontal pleiotropy was observed.Conclusion: This MR study provides genetic evidence suggesting a causal association between asthma and the risk of AF and HF, although not at the level of significance after multiple testing correction. Programs aimed at treating asthma among asthmatics might help prevent the adverse health effects inflicted by CVDs.

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Shared Genetic Liability and Causal Associations Between Major Depressive Disorder and Cardiovascular Diseases

Cited by 28 publications

References 78 publications

Causal Association and Shared Genetics Between Asthma and COVID-19

Causal Association and Shared Genetics Between Asthma and COVID-19

Assessment of causal associations between handgrip strength and cardiovascular diseases: A two sample mendelian randomization study

Genetic liability to asthma and risk of cardiovascular diseases: A Mendelian randomization study

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