Cannabis Use and the Risk of Cardiovascular Diseases: A Mendelian Randomization Study.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhao J
PROVIDER: S-EPMC8366226 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundThe use of cannabis has increased globally due to more regions decriminalizing marijuana use for therapeutic and recreational aims. Several observational studies have revealed that cannabis use is associated with an increased risk of adverse cardiovascular pathologies and diseases. Nevertheless, the causal associations between cannabis use and cardiovascular diseases remain unclear. Hence, we performed single-variable and multivariable Mendelian randomization (MR) to evaluate the association between cannabis use disorder and various cardiovascular diseases.Materials and methodsSummary statistics were collected from the largest-to-date genome-wide association studies (GWAS) of cannabis use disorder. The 12 SNPs for cannabis use disorder were used as instrumental variables in this study. MR estimates were pooled using a random-effects inverse-variance weighted (IVW) method. Simple median and weighted median methods were conducted as sensitivity analyses.ResultsThe genetic liability to cannabis use disorder was associated with an augmented risk of coronary artery disease, myocardial infarction, atrial fibrillation, heart failure, deep venous thrombosis, pulmonary embolism, and stroke. Except for stroke, the results were inconsistent in the sensitivity analyses. The overall patterns for the associations of cannabis use disorder with atrial fibrillation, heart failure, pulmonary embolism and stroke remained in multivariable MR analyses adjusting for potential mediators, including smoking, alcohol, body mass index, blood lipid, type 2 diabetes, hypertension, and depression. However, the association with coronary artery disease, myocardial infarction, and deep venous thrombosis did not persist in multivariable MR analyses. Mediation analysis demonstrated that smoking, body mass index, low-density lipoprotein, hypertension, and depression have more significant mediation effects, which suggests that these factors partly mediate the link from cannabis use disorder to coronary artery disease, myocardial infarction, and deep venous thrombosis.ConclusionThe genetic liability to cannabis use disorder was associated with a higher risk of atrial fibrillation, heart failure, pulmonary embolism, and stroke. The evidence for the association between cannabis use disorder, coronary artery disease, myocardial infarction, and deep venous thrombosis was weak. Hence, future use of cannabis for therapeutic and recreational aims should consider its potential impact on cardiovascular diseases.
| S-EPMC9582269 | biostudies-literature
Project description:BackgroundAssociation between cannabis use and development of atherosclerotic cardiovascular disease (ASCVD) is inconsistent and challenging to interpret, given existing study limitations.MethodsSixty five independent single-nucleotide polymorphisms (SNPs), obtained from a genome-wide association study on lifetime cannabis use, were employed as genetic instruments to estimate the effects of genetically indexed cannabis use on risk of coronary artery disease (CAD) and acute ischemic stroke (IS) using a two-sample Mendelian randomization (MR) approach. Summary statistics on CAD (CARDIoGRAMplusC4D; 60,801 cases and 123,504 controls) and IS (MEGASTROKE; 34,217 cases and 406,111 controls) were obtained separately. A comprehensive review of the observational literature on cannabis use and CAD or IS was also performed and contrasted with MR results.ResultsThere was no causal effect of cannabis use on the risk of CAD (odds ratio (OR) per ever-users vs. never-users 0.93; 95% confidence interval (CI), 0.83 to 1.03) or IS (OR 1.05; 95%CI, 0.93 to 1.19). Sensitivity analyses yielded similar results, and no heterogeneity and directional pleiotropy was observed. Our meta-analysis of observational studies showed no significant association between ever use of cannabis with risk of CAD (k = 6 studies; ORpooled = 1.23, 95%CI 0.78 to 1.69), nor with IS (k = 6 studies; ORpooled = 1.22, 95%CI 0.95 to 1.50).ConclusionUsing a genetic approach approximating a clinical trial does not provide evidence consistent with a causal effect of genetic predisposition to cannabis use on CAD or IS development. Further studies are needed to replicate our findinds, an to investigate more precisely the risk of ASCVD in relation to the quantity, type, route of administration, or the age at exposure to cannabis.
| S-EPMC10717446 | biostudies-literature
Project description:Cannabis use is observationally associated with an increased risk of schizophrenia, but whether the relationship is causal is not known. Using a genetic approach, we took 10 independent genetic variants previously identified to associate with cannabis use in 32 330 individuals to determine the nature of the association between cannabis use and risk of schizophrenia. Genetic variants were employed as instruments to recapitulate a randomized controlled trial involving two groups (cannabis users vs nonusers) to estimate the causal effect of cannabis use on risk of schizophrenia in 34 241 cases and 45 604 controls from predominantly European descent. Genetically-derived estimates were compared with a meta-analysis of observational studies reporting ever use of cannabis and risk of schizophrenia or related disorders. Based on the genetic approach, use of cannabis was associated with increased risk of schizophrenia (odds ratio (OR) of schizophrenia for users vs nonusers of cannabis: 1.37; 95% confidence interval (CI), 1.09-1.67; P-value=0.007). The corresponding estimate from observational analysis was 1.43 (95% CI, 1.19-1.67; P-value for heterogeneity =0.76). The genetic markers did not show evidence of pleiotropic effects and accounting for tobacco exposure did not alter the association (OR of schizophrenia for users vs nonusers of cannabis, adjusted for ever vs never smoker: 1.41; 95% CI, 1.09-1.83). This adds to the substantial evidence base that has previously identified cannabis use to associate with increased risk of schizophrenia, by suggesting that the relationship is causal. Such robust evidence may inform public health messages about cannabis use, especially regarding its potential mental health consequences.
| S-EPMC5984096 | biostudies-literature
Project description:BackgroundObservational studies suggested that multiple sclerosis (MS) is associated with cardiovascular diseases (CVDs). However, the causal association has not been fully elucidated. Thus, we aim to assess the causality of the associations of MS with risk of CVDs.MethodsA two-sample Mendelian randomization (MR) study was performed to explore the causality. Genetic instruments were identified for MS from a genome-wide association study (GWAS) involving 115,803 individuals. Summary-level data for CVDs were obtained from different GWAS meta-analysis studies. MR analysis was conducted mainly using the inverse-variance weighted (IVW) method. Sensitivity analyses were further performed to ensure the robustness of the results.ResultsThis MR study found suggestive evidence that genetic liability to MS was associated with an increased risk of coronary artery disease (CAD) [odds ratio (OR), 1.02; 95% confidence interval (CI), 1.00-1.04; p = 0.03], myocardial infarction (MI) (OR, 1.03; 95% CI, 1.00-1.06; p = 0.01), heart failure (HF) (OR, 1.02; 95% CI, 1.00-1.04; p = 0.02), all-cause stroke (AS) (OR, 1.02; 95% CI, 1.00-1.05; p = 0.02), and any ischemic stroke (AIS) (OR, 1.02; 95% CI, 1.00-1.05; p = 0.04). The null-association was observed between MS and the other CVDs. Further analyses found little evidence of pleiotropy.ConclusionsWe provided suggestive genetic evidence for the causal associations of MS with increased risk of CAD, MI, HF, AS, and AIS, which highlighted the significance of active monitoring and prevention of cardiovascular risk to combat cardiovascular comorbidities in MS patients.
| S-EPMC8964627 | biostudies-literature
Project description:BackgroundThe causal direction and magnitude of the associations between telomere length (TL) and cardiovascular diseases (CVDs) remain uncertain due to susceptibility of reverse causation and confounding. This study aimed to investigate the associations between TL and CVDs using Mendelian randomization (MR).Materials and methodsIn this two-sample MR study, we identified 154 independent TL-associated genetic variants from a genome-wide association study (GWAS) consisting of 472,174 individuals (aged 40-69) in the UK Biobank. Summary level data of CVDs were obtained from different GWASs datasets. Methods of inverse variance weighted (IVW), Mendelian Randomization-Egger (MR-Egger), Mendelian Randomization robust adjusted profile score (MR-RAPS), maximum likelihood estimation, weighted mode, penalized weighted mode methods, and Mendelian randomization pleiotropy residual sum and outlier test (MR-PRESSO) were conducted to investigate the associations between TL and CVDs.ResultsOur findings indicated that longer TL was significantly associated with decreased risk of coronary atherosclerosis [odds ratio (OR), 0.85; 95% confidence interval (CI), 0.75-0.95; P = 4.36E-03], myocardial infarction (OR, 0.72; 95% CI, 0.63-0.83; P = 2.31E-06), ischemic heart disease (OR, 0.87; 95% CI, 0.78-0.97; P = 1.01E-02), stroke (OR, 0.87; 95% CI, 0.79-0.95; P = 1.60E-03), but an increased risk of hypertension (OR, 1.12; 95% CI, 1.02-1.23; P = 2.00E-02). However, there was no significant association between TL and heart failure (OR, 0.94; 95% CI, 0.87-1.01; P = 1.10E-01), atrial fibrillation (OR, 1.01; 95% CI, 0.93-1.11; P = 7.50E-01), or cardiac death (OR, 0.95; 95% CI, 0.82-1.10; P = 4.80E-01). Both raw and outlier corrected estimates from MR-PRESSO were consistent with those of IVW results. The sensitivity analyses showed no evidence of pleiotropy (MR-Egger intercept, P > 0.05), while Cochran's Q test and MR-Egger suggested different degrees of heterogeneity.ConclusionOur MR study suggested that longer telomeres were associated with decreased risk of several CVDs, including coronary atherosclerosis, myocardial infarction, ischemic heart disease, and stroke, as well as an increased risk of hypertension. Future studies are still warranted to validate the results and investigate the mechanisms underlying these associations.
| S-EPMC9637552 | biostudies-literature
Project description: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.
| S-EPMC9360591 | biostudies-literature
Project description:ImportanceSmoking is associated with atherosclerotic cardiovascular disease, but the relative contribution to each subtype (coronary artery disease [CAD], peripheral artery disease [PAD], and large-artery stroke) remains less well understood.ObjectiveTo determine the association between genetic liability to smoking and risk of CAD, PAD, and large-artery stroke.Design, setting, and participantsMendelian randomization study using summary statistics from genome-wide associations of smoking (UK Biobank; up to 462 690 individuals), CAD (Coronary Artery Disease Genome Wide Replication and Meta-analysis plus the Coronary Artery Disease Genetics Consortium; up to 60 801 cases, 123 504 controls), PAD (VA Million Veteran Program; up to 24 009 cases, 150 983 controls), and large-artery stroke (MEGASTROKE; up to 4373 cases, 406 111 controls). This study was conducted using summary statistic data from large, previously described cohorts. Review of those publications does not reveal the total recruitment dates for those cohorts. Data analyses were conducted from August 2019 to June 2020.ExposuresGenetic liability to smoking (as proxied by genetic variants associated with lifetime smoking index).Main outcomes and measuresRisk (odds ratios [ORs]) of CAD, PAD, and large-artery stroke.ResultsGenetic liability to smoking was associated with increased risk of PAD (OR, 2.13; 95% CI, 1.78-2.56; P = 3.6 × 10-16), CAD (OR, 1.48; 95% CI, 1.25-1.75; P = 4.4 × 10-6), and stroke (OR, 1.40; 95% CI, 1.02-1.92; P = .04). Genetic liability to smoking was associated with greater risk of PAD than risk of large-artery stroke (ratio of ORs, 1.52; 95% CI, 1.05-2.19; P = .02) or CAD (ratio of ORs, 1.44; 95% CI, 1.12-1.84; P = .004). The association between genetic liability to smoking and atherosclerotic cardiovascular diseases remained independent from the effects of smoking on traditional cardiovascular risk factors.Conclusions and relevanceIn this mendelian randomization analysis of data from large studies of atherosclerotic cardiovascular diseases, genetic liability to smoking was a strong risk factor for CAD, PAD, and stroke, although the estimated association was strongest between smoking and PAD. The association between smoking and atherosclerotic cardiovascular disease was independent of traditional cardiovascular risk factors.
| S-EPMC7816104 | biostudies-literature
Project description:Coffee consumption has been linked to a lower risk of cardiovascular disease in observational studies, but whether the associations are causal is not known. We conducted a Mendelian randomization investigation to assess the potential causal role of coffee consumption in cardiovascular disease. Twelve independent genetic variants were used to proxy coffee consumption. Summary-level data for the relations between the 12 genetic variants and cardiovascular diseases were taken from the UK Biobank with up to 35,979 cases and the FinnGen consortium with up to 17,325 cases. Genetic predisposition to higher coffee consumption was not associated with any of the 15 studied cardiovascular outcomes in univariable MR analysis. The odds ratio per 50% increase in genetically predicted coffee consumption ranged from 0.97 (95% confidence interval (CI), 0.63, 1.50) for intracerebral hemorrhage to 1.26 (95% CI, 1.00, 1.58) for deep vein thrombosis in the UK Biobank and from 0.86 (95% CI, 0.50, 1.49) for subarachnoid hemorrhage to 1.34 (95% CI, 0.81, 2.22) for intracerebral hemorrhage in FinnGen. The null findings remained in multivariable Mendelian randomization analyses adjusted for genetically predicted body mass index and smoking initiation, except for a suggestive positive association for intracerebral hemorrhage (odds ratio 1.91; 95% CI, 1.03, 3.54) in FinnGen. This Mendelian randomization study showed limited evidence that coffee consumption affects the risk of developing cardiovascular disease, suggesting that previous observational studies may have been confounded.
| S-EPMC8308456 | biostudies-literature
Project description:BackgroundPrevious researches have demonstrated a connection between psychiatric disorders and cardiovascular diseases (CVDs), but the cause-and-effect relationship is still unclear. To that goal, the mendelian randomization (MR) method was used to study the causal link between psychiatric disorders and CVDs.MethodsGenome-wide association studies (GWAS) data were collected for four CVDs, including coronary artery disease (n = 547,261), atrial fibrillation (n = 537,409), heart failure (n = 977,323) and ischemic stroke (n = 440,328). Summary data for four psychiatric disorders, including bipolar disorder (n = 51,710), major depressive disorder (n = 480,359), schizophrenia (n = 127,906) and attention deficit hyperactivity disorder (n = 55,374), came from the Psychiatric Genomics Consortium (PGC). All participants were European. The IVW method was mainly used, and the reliability of the results was increased using sensitivity analyses such as MR-Egger, Cochrane's Q test, MR-PRESSO and leave-one-out.ResultsMR revealed that the attention deficit hyperactivity disorder was linked to an increased risk of atrial fibrillation (OR, 1.085; 95% CI, 1.021-1.153; P = 0.008), heart failure (OR, 1.117; 95% CI, 1.044-1.195; P = 0.001), and ischemic stroke (OR, 1.146; 95% CI, 1.052-1.248; P = 0.002). The schizophrenia was linked to an increased risk of heart failure (OR, 1.035; 95% CI, 1.006-1.066; P = 0.017), but was found to be suggestively inverse associated with coronary artery disease (OR, 0.969; 95% CI, 0.941-0.997; P = 0.03). The major depressive disorder was associated with higher odds of coronary artery disease (OR, 1.109; 95% CI, 1.018-1.208; P = 0.018), while the bipolar disorder was linked to a reduced incidence of coronary artery disease (OR, 0.894; 95% CI, 0.831-0.961; P = 0.002) and heart failure (OR, 0.889; 95% CI, 0.829-0.955; P = 0.001). There were no clear relationships between other psychiatric disorders and CVDs.ConclusionThe results provide genetic proof of a possible causal relationship between psychiatric disorders and CVDs. These results imply that psychiatric disorders may be the cause of some CVDs, and that some abnormal mental states may increase or reduce the likelihood of CVDs, providing guidance for the CVDs prevention.
| S-EPMC10569997 | biostudies-literature
Project description:Previous intervention studies have shown some benefits of dark chocolate for the cardiovascular system, but it has not been established whether dark chocolate intake is associated with the risk of cardiovascular diseases (CVDs). To investigate the causality between dark chocolate intake and the risk of CVDs, a Mendelian randomization (MR) study was conducted. We obtained summary-level data on dark chocolate intake and CVDs from publicly available genome-wide association studies. In this MR study, the main approach was to use a fixed-effect model with inverse variance weighted (IVW) and evaluate the robustness of the results via sensitivity analysis. We found that dark chocolate intake was significantly associated with the reduction of the risk of essential hypertension (EH) (OR = 0.73; 95% CI 0.60-0.88; p = 1.06 × 10-3), as well as with the suggestive association to the reduced risk of venous thromboembolism (OR = 0.69; 95% CI 0.50-0.96; p = 2.81 × 10-2). However, no association was found between dark chocolate intake and the other ten CVDs. Our study provides evidence for a causality between dark chocolate intake and a reduced risk of EH, which has important implications for the prevention of EH in the population.
| S-EPMC10781976 | biostudies-literature