Associations between artificial sweetener intake from cereals, coffee, and tea and the risk of type 2 diabetes mellitus: A genetic correlation, mediation, and mendelian randomization analysis
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SUBMITTER: Zhang Y
PROVIDER: S-EPMC10849235 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundExisting studies on the relationship between tea intake and lung diseases have yielded inconsistent results, leading to an ongoing dispute on this issue. The impact of tea consumption on the respiratory system remained elucidating.Materials and methodsWe conducted a two-sample Mendelian randomization (MR) study to evaluate the associations between five distinct tea intake phenotypes and 15 different respiratory outcomes using open Genome-wide association study (GWAS) data. The inverse variance weighted (IVW) was used for preliminary screening and a variety of complementary methods were used as sensitivity analysis to validate the robustness of MR estimates. Pathway enrichment analysis was used to explore possible mechanisms.ResultsIVW found evidence for a causal effect of standard tea intake on an increased risk of lung squamous cell cancer (LSCC) (OR = 1.004; 95% CI = 1.001-1.007; P = 0.00299). No heterogeneity or pleiotropy was detected. After adjustment for potential mediators, including smoking, educational attainment, and time spent watching television, the association was still robust in multivariable MR. KEGG and GO enrichment predicted proliferation and activation of B lymphocytes may play a role in this causal relation. No causalities were observed when evaluating the effect of other kinds of tea intake on various pulmonary diseases.ConclusionOur MR estimates provide causal evidence of the independent effect of standard tea intake (black tea intake) on LSCC, which may be mediated by B lymphocytes. The results implied that the population preferring black tea intake should be wary of a higher risk of LSCC.
| S-EPMC10875148 | biostudies-literature
Project description:The relationship between the intake of artificial sweetener (AS) and adverse pregnancy outcomes is under-researched, and existing studies yield inconsistent conclusions. A Mendelian randomization (MR) approach was employed to investigate the causal relationship between the intake of AS and adverse pregnancy outcomes. Instrumental variables related to the exposure phenotype were selected for analysis. The analysis was conducted using genome-wide association study summary data from public datasets. The inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode methods were used to evaluate the causal relationship between exposure and outcomes. Sensitivity analysis and multivariable Mendelian randomization enrolling body mass index, type 2 diabetes mellitus, and fasting glucose were employed to further validate the consistency and robustness of the results. In univariable MR, the intake of AS added to tea was associated with an increased risk of ectopic pregnancy [OR = 1.821 (1.118-2.967), p = 0.016]. In multivariable MR adjusting for body mass index and type 2 diabetes mellitus, the intake of AS added to cereal was linked to a reduced risk of ectopic pregnancy [OR = 0.361 (0.145-0.895), p = 0.028] and premature rupture of membranes [OR = 0.116 (0.019-0.704), p = 0.019], while the intake of artificial sweetener added to coffee was associated with an increased risk of placenta previa [OR = 1.617 (1.042-2.510), p = 0.032]. No causal relationship was identified between the intake of artificial sweetener and other adverse pregnancy outcomes. The consumption of artificial sweetener during pregnancy warrants careful consideration.
| S-EPMC11479087 | biostudies-literature
Project description:Rationale and objectiveA causal relationship concerning coffee intake and diabetic nephropathy (DN) is controversial. We conducted a Mendelian randomization study to assess the causal nature of these associations.Methods40 independent single nucleotide polymorphisms (SNPs) associated with coffee intake were selected from the UK Biobank study. Summary-level data for diabetic nephropathy were obtained from publicly available genome-wide association studies (GWAS) and the FinnGen consortium. Inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods were used to examine a causal association. Sensitivity analyses included Cochran's Q test, the intercept of MR-Egger, MR-PRESSO, and the Outlier method. Leave-One-Out sensitivity analyses were also conducted to reduce the heterogeneity.ResultsOur current study demonstrated positive associations of genetically predicted coffee intake with diabetic nephropathy (OR=1.939; P = 0.045 and type 2 diabetes with renal complications (OR = 2.787, P= 0.047). These findings were robust across several sensitivity analyses.ConclusionsThis study found a positive correlation between coffee consumption and the risk of diabetic nephropathy using genetic data. For a more accurate and trustworthy conclusion, subgroup analysis on coffee intake, including preparing method, variety of coffee, and quantity, is required.
| S-EPMC10352828 | biostudies-literature
Project description:Epidemiological studies have suggested green tea intake was associated with a reduced risk of Parkinson's disease (PD). However, whether green tea intake has an effect on PD progression is unknown. To evaluate the role of green tea intake in PD progression, we conducted a two-sample Mendelian randomization analysis using summary statistics from genome-wide association studies of green tea intake (N = 64,949), age at onset (N = 28,568) and progression (N = 4,093) of PD. One standard deviation increase in genetically determined green tea intake was significantly associated with slower progression to dementia (OR: 0.87, 95% CI: 0.81-0.94, P: 3.48E-04) after the Bonferroni correction. Meanwhile, higher green tea intake was nominally associated with slower progression to depression, and lower risk of dementia, depression, hyposmia and insomnia at baseline. The results were robust under all sensitivity analyses. These results might facilitate novel therapeutic targets to slow down the progression of PD in clinical trials, and have clinical implications for patients with PD.
| S-EPMC9199515 | biostudies-literature
Project description:BackgroundIn observational studies, the relationship between coffee intake and bone mineral density (BMD) is contradictory. However, residual confounding tends to bias the results of these studies. Therefore, we used a two-sample Mendelian randomization (MR) approach to further investigate the potential causal relationship between the two.MethodsGenetic instrumental variables (IVs) associated with coffee intake were derived from genome-wide association studies (GWAS) of the Food Frequency Questionnaire (FFQ) in 428,860 British individuals and matched using phenotypes in PhenoScanner. Summarized data on BMD were obtained from 537,750 participants, including total body BMD (TB-BMD), TB-BMD in five age brackets ≥60, 45-60, 30-45, 15-30, and 0-15 years, and BMD in four body sites: the lumbar spine, the femoral neck, the heel, and the ultradistal forearm. We used inverse variance weighting (IVW) methods as the primary analytical method for causal inference. In addition, several sensitivity analyses (MR-Egger, Weighted median, MR-PRESSO, Cochran's Q test, and Leave-one-out test) were used to test the robustness of the results.ResultsAfter Bonferroni correction, Coffee intake has a potential positive correlation with total body BMD (effect estimate [Beta]: 0.198, 95% confidence interval [Cl]: 0.05-0.35, P=0.008). In subgroup analyses, coffee intake was potentially positively associated with TB-BMD (45-60, 30-45 years) (Beta: 0.408, 95% Cl: 0.12-0.69, P=0.005; Beta: 0.486, 95% Cl: 0.12-0.85, P=0.010). In addition, a significant positive correlation with heel BMD was also observed (Beta: 0.173, 95% Cl: 0.08-0.27, P=0.002). The results of the sensitivity analysis were generally consistent.ConclusionThe results of the present study provide genetic evidence for the idea that coffee intake is beneficial for bone density. Further studies are needed to reveal the biological mechanisms and offer solid support for clinical guidelines on osteoporosis prevention.
| S-EPMC10987693 | biostudies-literature
Project description:Observational studies have yielded conflicting results regarding the relationship between tea intake and migraine risk. Residual confounders and potential reverse causality are unavoidable in traditional observational studies. To provide evidence for establishing viable disease screening and prevention strategies, a Mendelian randomization study (MR) was conducted to determine the causal inference between tea intake and migraine. We obtained 28 single-nucleotide polymorphisms (SNPs) for any migraine (AM), 25 SNPs for migraine with aura (MA), and 27 SNPs for migraine without aura (MO) associated with tea intake derived from a large genome-wide association study (GWAS) of the UK Biobank (UKBB) (containing 447,485 samples). The largest migraine GWAS performed by the International Headache Genetics Consortium (IHGC), including 29,209 cases and 172,931 controls, provided data on migraines and their subtypes (MA and MO). We used the method of inverse variance weighting (IVW) with fixed effects as the first-string MR selection. Sensitivity analysis and MR-pleiotropy residual sum and outlier (MR-PRESSO) method further assessed the robustness of the findings. Based on the conclusion of IVW in the fixed effects model, we found that tea intake had no causal relationship with AM risk (odds ratio (OR), 0.94; 95% confidence interval (CI), 0.70-1.25; P = 0.65), MA risk (OR, 0.93; 95% CI, 0.51-1.72; P = 0.83), or MO risk (OR, 0.90; 95% CI, 0.52-1.54; P = 0.69). Sensitivity analyses and MR-PRESSO showed no directional pleiotropy or heterogeneity. Our two-sample MR investigation found no causality between tea intake and migraine risk in European populations, implying that attempts to change tea drinking habits may not lead to a reduced risk of migraine.
| S-EPMC10412590 | biostudies-literature
Project description:BackgroundAlthough studies suggest that tea consumption is associated with a reduced risk of cardiovascular disease (CVD). There is no unified conclusion about the potential relationship between tea drinking and CVD. We used a two-sample Mendelian randomized (MR) analysis to systematically explore the causal relationship between tea intake and CVD subtypes for the first time. Furthermore the mediating effect of hypertension was also explored by a two-step MR.MethodsGenetic instruments for tea intake were identified from a genome-wide association studies (GWAS) involving 447,485 people. Summary data on cardio-vascular disease came from different GWAS meta-analysis studies. In the first step we explored the causal effect of tea intake and CVD. In the second step, we examined the association of hypertension with heart failure and ischemic stroke and estimated the mediating effect of hypertension. Inverse variance weighted MR analysis was used as the primary method for causal analysis. A further sensitivity analysis was performed to ensure robustness of the results.ResultsOne standard deviation increase in tea intake was associated with a 25% (OR = 0.75, 95%CI = 0.61-0.91, p = 0.003) lower risk of hypertension, a 28% (OR = 0.72, 95%CI = 0.58-0.89, p = 0.002) lower risk of heart failure, and a 29% (OR = 0.71, 95%CI = 0.55-0.92, p = 0.008) lower risk of ischemic stroke, respectively. And the association between tea drinking and the risk of heart failure and ischemic stroke may be mediated by hypertension. Sensitivity analyses found little evidence of pleiotropy.ConclusionOur two-sample MR analysis provided genetic evidence that tea intake was significantly associated with a reduced risk of hypertension, heart failure, and ischemic stroke, and that hypertension may be a potential mediator. Further large randomized controlled trials should be conducted to confirm the causal effect of tea consumption on cardiovascular disease risk.
| S-EPMC9548982 | 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:Objective: Several observational studies have suggested that coffee consumption is associated with a lower risk of bladder cancer. However, observational studies are susceptible to confounding factors and reverse causality. We used a two-sample Mendelian randomization (MR) method to assess the causal nature of this association. Methods: At the genome-wide significance level (p < 5 × 10-8), 12 single nucleotide polymorphisms (SNPs) strongly associated with coffee consumption were used as instrumental variables (IVs). Summary-level data on genetic variation in bladder cancer were obtained from the United Kingdom biobank (420,838 samples) and FinnGen consortium (175,121 samples). Multiple MR methods were used. Heterogeneity and horizontal pleiotropy were detected using Cochran's Q test and MR-Egger. Results: Twelve SNPs were included in the primary analysis. After excluding 8 SNPs with potential secondary phenotypes, the remaining 4 SNPs were included in the sensitivity analysis. In all analyses, Cochran's Q statistic indicated that there was no heterogeneity among SNPs, and the MR-Egger analysis did not reveal the existence of horizontal pleiotropy (p > 0.05). In the United Kingdom Biobank, the odds ratio (OR) for bladder cancer was 1.022 (95% confidence interval (CI), 0.679-1.537) for per 50% increase in coffee consumption. Consistent results were obtained in the FinnGen consortium (OR = 0.890, 95% CI, 0.467-1.697). Sensitivity analysis showed consistent results with primary analysis. Conclusion This study does not support a causal association between habitual coffee consumption and bladder cancer risk.
| S-EPMC9565034 | biostudies-literature
Project description:Background: Gout, an increasingly prevalent form of inflammatory arthritis, is caused by the accumulation of uric acid crystals in joints, resulting in severe pain, swelling and stiffness that adversely affect physical, mental and emotional wellbeing. The management of gout requires a combination of medication and lifestyle modifications. Recent studies suggest that tea intake may reduce the risk of developing gout; however, further research is needed to establish a causal relationship. Methods: In this study, we employed a bidirectional two-sample Mendelian randomization (MR) approach, utilizing genome-wide association study (GWAS) summary statistics, to investigate the causal association between increased tea intake and gout. We meticulously selected instrumental variables (IVs) based on rigorous criteria and employed five different MR methods. Heterogeneity was assessed using Cochran's Q statistic, and pleiotropy was evaluated using the MR Egger intercept and MR-PRESSO tests. Weak IVs were identified using F values. The Phenoscanner database was consulted to exclude single nucleotide polymorphisms associated with confounding factors or outcomes. Results: The study included one dataset related to tea intake (ukb-b-6066) and three datasets related to gout (ukb-b-12765, finn-b-M13_GOUT, and finn-b-GOUT_STRICT). Our forward MR analysis suggest a causal relationship between increased tea intake and reduced risk of gout in all three gout-related datasets [OR (95% CI): 0.9966 (0.9938-0.9993), p = 0.0167; 0.4842 (0.2683-0.8737), p-value = 0.0160; and 0.4554 (0.2155-0.9623), p = 0.0393, respectively]. The reveres MR showed increased risk of gout (ukb-b-12765) was significantly associated with low tea intake according to the IVW analysis [OR (95% CI): 0.0062 (0.0002-0.154), p = 0.0020]. However, this association was not observed in the Finn-b-M13_GOUT and Finn-b-GOUT_STRICT [OR (95% CI): 0.9992 (0.9909-1.0075), p = 0.8453 and OR (95% CI): 0.9996 (0.9932-1.0059), p = 0.8896, respectively]. No significant heterogeneity or potential pleiotropy was detected, and the possibility of weak IVs was also excluded. Conclusion: Our MR analysis suggest a causal relationship between genetically predicted tea intake and a decreased risk of gout. These findings underscore the potential advantages of increasing tea intake for preventing gout. However, further research is needed to validate these results and elucidate the underlying mechanisms.
| S-EPMC10374259 | biostudies-literature