Coffee Consumption and Cardiovascular Diseases: A Mendelian Randomization Study.
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ABSTRACT:
SUBMITTER: Yuan S
PROVIDER: S-EPMC8308456 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundCoffee is one of the most consumed beverages in the world, coffee consumption has been growing in the United States over the past 20 years. Periodontitis is defined by the pathologic loss of the periodontal ligament and destruction of the connective tissue attachment and alveolar bone loss and is related to different systemic diseases and conditions. However, the causality has remained unclarified, thus we regarded discovering the causal relationship between coffee consumption and the liability to periodontitis as the objective of the study.MethodsCoffee consumption was subdivided into binary coffee consumption and continuous coffee consumption to refine the study design. Genetic instruments were stretched from the MRC-IEU's (MRC Integrative Epidemiology Unit) output from the GWAS pipeline using phesant-derived variables based on the UK Biobank, the Gene-Lifestyle Interactions in Dental Endpoints (GLIDE) project, and the joint meta-analysis of a recent GWAS. The IVW (Inverse Variance Weighted) was regarded as the primary method to estimate the causality, a scatter plot revealed the intuitive result, and tests for stability were also carried out.ResultsAn effect of continuous coffee consumption on the risk of periodontitis was found, with per SD of coffee consumed increases, the risk of periodontitis rises by 1.04% (Odds Ratio of IVW is 1.0104), while the effect of binary coffee consumption on periodontitis did not meet the requirement of indicating a strong causal association, neither were the reverse causality analyses.ConclusionsThe study indicated the causality of continuous coffee consumption to the risk of periodontitis with a relatively small scale of effect estimate and no strong evidence for an effect of binary coffee-consuming behavior on periodontitis. There was also no intensive evidence suggesting reverse causality.
| S-EPMC10492363 | biostudies-literature
Project description:Habitual coffee and caffeine consumption has been reported to be associated with numerous health outcomes. This perspective focuses on Mendelian Randomization (MR) approaches for determining whether such associations are causal. Genetic instruments for coffee and caffeine consumption are described, along with key concepts of MR and particular challenges when applying this approach to studies of coffee and caffeine. To date, at least fifteen MR studies have investigated the causal role of coffee or caffeine use on risk of type 2 diabetes, cardiovascular disease, Alzheimer's disease, Parkinson's disease, gout, osteoarthritis, cancers, sleep disturbances and other substance use. Most studies provide no consistent support for a causal role of coffee or caffeine on these health outcomes. Common study limitations include low statistical power, potential pleiotropy, and risk of collider bias. As a result, in many cases a causal role cannot confidently be ruled out. Conceptual challenges also arise from the different aspects of coffee and caffeine use captured by current genetic instruments. Nevertheless, with continued genome-wide searches for coffee and caffeine related loci along with advanced statistical methods and MR designs, MR promises to be a valuable approach to understanding the causal impact that coffee and caffeine have in human health.
| S-EPMC6213346 | biostudies-literature
Project description:BackgroundObservational studies have reported either null or weak protective associations for coffee consumption and risk of breast cancer.MethodsWe conducted a two-sample Mendelian randomization (MR) analysis to evaluate the relationship between coffee consumption and breast cancer risk using 33 single-nucleotide polymorphisms (SNPs) associated with coffee consumption from a genome-wide association (GWA) study on 212,119 female UK Biobank participants of White British ancestry. Risk estimates for breast cancer were retrieved from publicly available GWA summary statistics from the Breast Cancer Association Consortium (BCAC) on 122,977 cases (of which 69,501 were estrogen receptor (ER)-positive, 21,468 ER-negative) and 105,974 controls of European ancestry. Random-effects inverse variance weighted (IVW) MR analyses were performed along with several sensitivity analyses to assess the impact of potential MR assumption violations.ResultsOne cup per day increase in genetically predicted coffee consumption in women was not associated with risk of total (IVW random-effects; odds ratio (OR): 0.91, 95% confidence intervals (CI): 0.80-1.02, P: 0.12, P for instrument heterogeneity: 7.17e-13), ER-positive (OR = 0.90, 95% CI: 0.79-1.02, P: 0.09) and ER-negative breast cancer (OR: 0.88, 95% CI: 0.75-1.03, P: 0.12). Null associations were also found in the sensitivity analyses using MR-Egger (total breast cancer; OR: 1.00, 95% CI: 0.80-1.25), weighted median (OR: 0.97, 95% CI: 0.89-1.05) and weighted mode (OR: 1.00, CI: 0.93-1.07).ConclusionsThe results of this large MR study do not support an association of genetically predicted coffee consumption on breast cancer risk, but we cannot rule out existence of a weak association.
| S-EPMC7815134 | biostudies-literature
Project description:BackgroundThe causal role of alcohol consumption for cardiovascular disease remains unclear. We used Mendelian randomization (MR) to predict the effect of alcohol consumption on 8 cardiovascular diseases.MethodsUp to 94 single-nucleotide polymorphisms were used as instrumental variables for alcohol consumption. Genetic association estimates for cardiovascular diseases were obtained from large-scale consortia and UK Biobank. Analyses were conducted using the inverse variance-weighted, weighted median, MR-PRESSO, MR-Egger, and multivariable MR methods.ResultsGenetically predicted alcohol consumption was consistently associated with stroke and peripheral artery disease across the different analyses. The odds ratios (ORs) per 1-SD increase of log-transformed alcoholic drinks per week were 1.27 ([95% CI, 1.12-1.45] P=2.87×10-4) for stroke and 3.05 ([95% CI, 1.92-4.85] P=2.30×10-6) for peripheral artery disease in the inverse variance-weighted analysis. There was some evidence for positive associations of genetically predicted alcohol consumption with coronary artery disease (OR, 1.16 [95% CI, 1.00-1.36]; P=0.052), atrial fibrillation (OR, 1.17 [95% CI, 1.00-1.37]; P=0.050), and abdominal aortic aneurysm (OR, 2.60 [95% CI, 1.15-5.89]; P=0.022) in the inverse variance-weighted analysis. These associations were somewhat attenuated in multivariable MR analysis adjusted for smoking initiation. There was no evidence of associations of genetically predicted alcohol consumption with heart failure (OR, 1.00 [95% CI, 0.68-1.47]; P=0.996), venous thromboembolism (OR, 1.04 [95% CI, 0.77-1.39]; P=0.810), and aortic valve stenosis (OR, 1.03 [95% CI, 0.56-1.90]; P=0.926).ConclusionsThis study provides evidence of a causal relationship between higher alcohol consumption and increased risk of stroke and peripheral artery disease. The causal role of alcohol consumption for other cardiovascular diseases requires further research.
| S-EPMC7299220 | biostudies-literature
Project description:BackgroundClozapine is an effective antipsychotic medication for patients with treatment-resistant schizophrenia. Previous studies revealed that smoking, alcohol intake, and coffee consumption altered the metabolism of clozapine. However, causal associations between substance use and clozapine levels were not sufficiently established.MethodsSeveral genome-wide association studies provided genetic tools for six measures of substance use, including age of smoking, cigarettes per day, smoking cessation, smoking initiation, coffee consumption, and alcohol consumption (GWASs). Utilizing the CLOZUK consortium's dataset, their associations with clozapine and its metabolite concentrations were evaluated. All GWAS data were collected from the European population. Mendelian randomization (MR) estimations from each genetic test were combined using inverse variance weighted (IVW) meta-analysis in combination with complementing techniques (such as weighted median and MR Egger). We also analyze horizontal pleiotropy and heterogeneity using various sensitivity analyses.ResultsGenetically predicted higher level of smoking initiation was significantly associated with reduced clozapine (β = -0.14, P = 4.53E-04) concentrations and norclozapine concentrations (β = -0.14, P = 3.33E-04), and increased coffee consumption was significantly associated with lower level of clozapine concentrations (β = -0.42, P = 1.70E-14), norclozapine concentrations (β = -0.27, P = 1.51E-07), and the metabolic ratio of clozapine to norclozapine (β = -0.15, P = 5.35E-07), survived after the Bonferroni correction (P = 0.05/6 = 0.008). In sensitivity analyses, the weighted median and MR Egger methods demonstrated directionally consistent effects. In addition, our sensitive test indicated no significant horizontal pleiotropy and heterogeneity (P > 0.05). However, other measures of substance use (age of initiation smoking, cigarettes per day, smoking cessation, and drinks per week) were not associated with clozapine metabolism.ConclusionOur investigation revealed a correlation between greater smoking initiation and coffee consumption and reduced blood levels of clozapine and norclozapine. Providing clinicians with guidance on how to adjust clozapine levels for clozapine-treated patients.
| S-EPMC9559606 | biostudies-literature
Project description:Background & aimThe association between habitual coffee or caffeine consumption and age at onset (AAO) of Huntington's disease (HD) is unclear. We employed Mendelian randomization to investigate the causal relationship between coffee consumption and AAO of HD.MethodsThe instrumental variable including 14 independent genetic variants associated with coffee consumption was selected from a genome-wide association study (GWAS) meta-analysis of 375,833 individuals of European ancestry. Genetic association estimates for AAO of HD were obtained from the Genetic Modifiers of Huntington's Disease Consortium GWAS meta-analysis including 9064 HD patients of European ancestry. The inverse variance weighted method was used to evaluate the causal estimate and a comprehensive set of analyses tested the robustness of our results.ResultsGenetically predicted higher coffee consumption was associated with an earlier AAO of HD (β = -1.84 years, 95% confidence interval = -3.47 to -0.22, P = 0.026). Results were robust to potential pleiotropy and weak instrument bias.ConclusionsThis genetic study suggests high coffee consumption is associated with an earlier AAO of HD. Coffee is widely consumed and thus our findings, if confirmed, offers a potential way to delay the onset of this debilitating autosomal dominant disease.
| S-EPMC10547005 | 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:Background and Aims: Coffee consumption has been suggested to increase the risk of migraine. However, causality remains inconclusive. In the present study, we performed a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between coffee consumption and migraine. Methods: We obtained nine single-nucleotide polymorphisms (SNPs) associated with coffee consumption at genome-wide significance (p < 5 × 10-8) from a large genome-wide association study (GWAS) based on the UK Biobank study (included 375,833 individuals). Summary-level data for any migraine (AM) and its subtypes (migraine with aura (MA) and migraine without aura (MO)) were obtained from the largest available GWAS of migraine conducted by the International Headache Genetics Consortium (IHGC) (included 59,674 cases and 316,078 controls). MR estimates were pooled using fixed-effect inverse-variance weighted (IVW) as the main method. Sensitivity analyses were further performed using weighted median, MR-Egger, and MR-PRESSO to assess the robustness of our findings. Results: Genetically-predicted 50% increase of coffee consumption was not causally associated with the risk of AM (odds ratio (OR), 0.97; 95% confidence interval (CI), 0.83-1.14; p = 0.71), MA (OR, 0.81; 95%CI, 0.58, 1.12; p = 0.19), or MO (OR, 0.97; 95%CI, 0.72, 1.30; p = 0.83) in the fixed-effect IVW methods. Sensitivity analyses returned similar results. No directional pleiotropy was found. Conclusion: This MR study does not support a causal relationship between genetically predicted coffee consumption and the risk of migraine. Coffee consumption is likely not a trigger nor a prevention strategy for migraine headaches.
| S-EPMC8822146 | biostudies-literature
Project description:BackgroundThe association between coffee and caffeine consumption and the risk of renal cell carcinoma was inconsistent among observational studies, and whether these observed associations were causal remained unclear. Therefore, we performed two-sample Mendelian randomization (MR) study to assess the causal nature of the association.Materials and methodsIn this study, 12 and two independent single nucleotide polymorphisms (SNPs) related to coffee and caffeine consumption at a genome-wide significance level of p < 5 × 10-8 were used as instrumental variables (IVs), respectively. Summary-level data for renal cell carcinoma were taken from the FinnGen consortium with up to 174,977 individuals, and the International Agency for Research on Cancer (IARC) with 13,230 individuals. We used inverse-variance weighted (IVW) as the main method, followed by the weighted median method, the MR-Egger regression method, and the MR robust adjusted profile score method. Outlier and pleiotropic variants were assessed by the MR Pleiotropy RESidual Sum and Outlier test and MR-Egger regression. We used meta-analysis methods in fixed-effects to combine the estimates from the two sources.ResultsThe genetically predicted coffee consumption was not associated with the risk of renal cell carcinoma in the FinnGen consortium, and the relationship was consistent in the IARC consortium. The pooled odds ratio (OR) per 50% increase of coffee consumption was 0.752 [95% confidence interval (CI), 0.512-1.105; p = 0.147]. In addition, complementary analyses that separated the coffee-related SNPs according to their relationship with blood levels of caffeine metabolites (higher, lower, or unrelated) found no relationship with renal cell carcinoma. The results were consistent after excluding eight SNPs due to potential risk factors at genome-wide significance (p < 5 × 10-8). Moreover, genetically predicted per 80-mg increase in caffeine consumption was not associated with the risk of renal cell carcinoma (pooled OR = 0.872, 95% CI: 0.676-1.125, p = 0.292).ConclusionOur MR study provided no convincing evidence for a causal effect between coffee and caffeine consumption and the risk of renal cell carcinoma. The associations for renal cell carcinoma need to be verified in well-powered studies.
| S-EPMC9441794 | biostudies-literature
Project description:BackgroundThere is evidence for a positive relationship between cigarette and coffee consumption in smokers. Cigarette smoke increases metabolism of caffeine, so this may represent a causal effect of smoking on caffeine intake.MethodsWe performed Mendelian randomization analyses in the UK Biobank (N = 114 029), the Norwegian HUNT study (N = 56 664) and the Copenhagen General Population Study (CGPS) (N = 78 650). We used the rs16969968 genetic variant as a proxy for smoking heaviness in all studies and rs4410790 and rs2472297 as proxies for coffee consumption in UK Biobank and CGPS. Analyses were conducted using linear regression and meta-analysed across studies.ResultsEach additional cigarette per day consumed by current smokers was associated with higher coffee consumption (0.10 cups per day, 95% CI: 0.03, 0.17). There was weak evidence for an increase in tea consumption per additional cigarette smoked per day (0.04 cups per day, 95% CI: -0.002, 0.07). There was strong evidence that each additional copy of the minor allele of rs16969968 (which increases daily cigarette consumption) in current smokers was associated with higher coffee consumption (0.16 cups per day, 95% CI: 0.11, 0.20), but only weak evidence for an association with tea consumption (0.04 cups per day, 95% CI: -0.01, 0.09). There was no clear evidence that rs16969968 was associated with coffee or tea consumption in never or former smokers or that the coffee-related variants were associated with cigarette consumption.ConclusionsHigher cigarette consumption causally increases coffee intake. This is consistent with faster metabolism of caffeine by smokers, but could also reflect a behavioural effect of smoking on coffee drinking.
| S-EPMC5837196 | biostudies-literature