The causal association between artificial sweeteners and the risk of cancer: a Mendelian randomization study.

Artificial sweeteners (ASs) have been widely added to food and beverages because of their properties of low calories and sweet taste. However, whether the consumption of ASs is causally associated with cancer risk is not clear. Here, we utilized the two-sample Mendelian randomization (MR) method to study the potential causal association. Genetic variants like single-nucleotide polymorphisms (SNPs) associated with exposure (AS consumption) were extracted from a genome-wide association study (GWAS) database including 64 949 Europeans and the influence of confounding was removed. The outcome was from 98 GWAS data and included several types of cancers like lung cancer, colorectal cancer, stomach cancer, breast cancer, and so on. The exposure-outcome SNPs were harmonized and then MR analysis was performed. The inverse-variance weighted (IVW) with random effects was used as the main analytical method accompanied by four complementary methods: MR Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses consisted of heterogeneity, pleiotropy, and leave-one-out analysis. Our results demonstrated that ASs added to coffee had a positive association with high-grade and low-grade serous ovarian cancer; ASs added to tea had a positive association with oral cavity and pharyngeal cancers, but a negative association with malignant neoplasm of the bronchus and lungs. No other cancers had a genetic causal association with AS consumption. Our MR study revealed that AS consumption had no genetic causal association with major cancers. Larger MR studies or RCTs are needed to investigate small effects and support this conclusion.

A genome-wide association study provides insights into the genetic etiology of 57 essential and non-essential trace elements in humans.

Trace elements are important for human health but may exert toxic or adverse effects. Mechanisms of uptake, distribution, metabolism, and excretion are partly under genetic control but have not yet been extensively mapped. Here we report a comprehensive multi-element genome-wide association study of 57 essential and non-essential trace elements. We perform genome-wide association meta-analyses of 14 trace elements in up to 6564 Scandinavian whole blood samples, and genome-wide association studies of 43 trace elements in up to 2819 samples measured only in the Trøndelag Health Study (HUNT). We identify 11 novel genetic loci associated with blood concentrations of arsenic, cadmium, manganese, selenium, and zinc in genome-wide association meta-analyses. In HUNT, several genome-wide significant loci are also indicated for other trace elements. Using two-sample Mendelian randomization, we find several indications of weak to moderate effects on health outcomes, the most precise being a weak harmful effect of increased zinc on prostate cancer. However, independent validation is needed. Our current understanding of trace element-associated genetic variants may help establish consequences of trace elements on human health.

Association of coffee intake with bone mineral density: a Mendelian randomization study.

Background: In 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. Methods: Genetic 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. Results: After 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. Conclusion: The 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.

Basal metabolic rate and the risk of urolithiasis: a two-sample Mendelian randomization study.

OBJECTIVE: Few studies have investigated the impact of basal metabolic rate (BMR) on the development of urolithiasis, and the causal relationship is yet to be established. In this study, a two-sample Mendelian randomization (MR) analysis was utilized to identify the causal relationship between BMR and risk of urolithiasis. METHOD: Genetic instruments for BMR were drawn from a public genome-wide association study (GWAS). Summary dates on BMR and urolithiasis were obtained from a GWAS meta-analysis with sample sizes of 454,874 and 212,453, respectively. The inverse-variance weighted (IVW) method was provided as the main approach to estimate the causal relationship. The weighted-median method and the MR-Egger method were used as supplements to the IVW method. In addition, we conducted sensitivity analyses, including heterogeneity tests, pleiotropy tests and leave-one-out analysis, to assess the robustness of the outcomes. Furthermore, the funnel plot asymmetry was visually inspected to evaluate possible bias. RESULTS: The inverse-variance weighted data revealed that genetically predicted BMR significantly decreased the risk of urolithiasis [beta coefficient (beta): - 0.2366, odds ratio (OR): 0.7893, 95% confidence interval (CI) 0.6504-0.9579, p = 0.0166]. CONCLUSIONS: BMR has causal effects on urolithiasis in an MR study, and the risk of urolithiasis in patients with lower levels of BMR is higher.

Iron Status and Risk of Heart Disease, Stroke, and Diabetes: A Mendelian Randomization Study in European Adults.

BACKGROUND: The relevance of iron status biomarkers for coronary artery disease (CAD), heart failure (HF), ischemic stroke (IS), and type 2 diabetes (T2D) is uncertain. We compared the observational and Mendelian randomization (MR) analyses of iron status biomarkers and hemoglobin with these diseases. METHODS AND RESULTS: Observational analyses of hemoglobin were compared with genetically predicted hemoglobin with cardiovascular diseases and diabetes in the UK Biobank. Iron biomarkers included transferrin saturation, serum iron, ferritin, and total iron binding capacity. MR analyses assessed associations with CAD (CARDIOGRAMplusC4D [Coronary Artery Disease Genome Wide Replication and Meta-Analysis Plus The Coronary Artery Disease Genetics], n=181 522 cases), HF (HERMES [Heart Failure Molecular Epidemiology for Therapeutic Targets), n=115 150 cases), IS (GIGASTROKE, n=62 100 cases), and T2D (DIAMANTE [Diabetes Meta-Analysis of Trans-Ethnic Association Studies], n=80 154 cases) genome-wide consortia. Observational analyses demonstrated J-shaped associations of hemoglobin with CAD, HF, IS, and T2D. In contrast, MR analyses demonstrated linear positive associations of higher genetically predicted hemoglobin levels with 8% higher risk per 1 SD higher hemoglobin for CAD, 10% to 13% for diabetes, but not with IS or HF in UK Biobank. Bidirectional MR analyses confirmed the causal relevance of iron biomarkers for hemoglobin. Further MR analyses in global consortia demonstrated modest protective effects of iron biomarkers for CAD (7%-14% lower risk for 1 SD higher levels of iron biomarkers), adverse effects for T2D, but no associations with IS or HF. CONCLUSIONS: Higher levels of iron biomarkers were protective for CAD, had adverse effects on T2D, but had no effects on IS or HF. Randomized trials are now required to assess effects of iron supplements on risk of CAD in high-risk older people.

Omega-3 fatty acids and their influence on hypertension and coronary atherosclerosis: Insights from a Mendelian randomization approach.

It has been suggested that Omega-3 fatty acids may improve endothelial thickness and thereby reduce the onset of cardiovascular diseases such as coronary atherosclerosis and hypertension. However, published observational epidemiological studies on the relationship between cardiovascular disease (CVD) and Omega-3 fatty acids remain inconclusive. Here, we performed a two-sample Mendelian randomisation analysis using publicly available GWAS pooled statistics to study a GWAS dataset of 16 380 466 SNPs in 23 363 cases and 195 429 controls (also of European ancestry) to determine genetic susceptibility to hypertension. We performed random-effects Inverse Variance Weighted (IVW) Mendelian Randomization (MR) analyses supplemented by a series of sensitivity assessments to measure the robustness of the findings and to detect any violations of the MR assumptions. During the course of the study, we used IVW, MR-Egger, and weighted median regression to infer that Omega-3 intake has a potentially adverse effect against atherosclerosis, although the trend was not significant (OR = 1.1198; 95%; CI: 0.9641-1.3006, p = .130). Meanwhile, our analyses showed a statistically significant negative association between Omega-3 fatty acid levels and risk of hypertension (OR = 0.9006; 95% CI: 0.8179-0.9917, p = .033). In addition, we explored the causal relationship between atherosclerosis and hypertension and found a significant correlation (OR = 1.3036; 95% CI: 1.0672-1.5923, p = .009). In conclusion, our extensive data investigated by MR suggest that elevated levels of Omega-3 fatty acids may be associated with an decreased risk of hypertension. Although there is no direct link between hypertension and atherosclerosis, the possibility of a subtle association cannot be categorically excluded.

Antidiabetic drug administration prevents bone mineral density loss: Evidence from a two-sample Mendelian randomization study.

The aim of this study was to investigate the effect of common antidiabetic drugs on BMD by two-sample Mendelian randomization (MR). The single nucleotide polymorphisms that were strongly associated with insulin, metformin, rosiglitazone and gliclazide were extracted as instrumental variables (IVs) for MR analysis. The inverse variance weighted (IVW) method was used as the primary MR method to assess the causal effect of antidiabetic drugs on BMD, and other MR methods, including Weighted median, MR Egger and Weighted mode, were used for complementary analysis. Reliability and stability were assessed by the leave-one-out test. In the present work, IVW estimation of the causal effect of insulin on heel BMD demonstrated that there was a null effect of insulin on heel BMD (ß = 0.765; se = 0.971; P = 0.430), while metformin treatment had a positive effect on heel BMD (ß = 1.414; se = 0.460; P = 2.118*10-3). The causal relationship between rosiglitazone and heel BMD analysed by IVW suggested that there was a null effect of rosiglitazone on heel BMD (ß = -0.526; se = 1.744; P = 0.763), but the causal effect of gliclazide on heel BMD evaluated by IVW demonstrated that there was a positive effect of gliclazide on heel BMD (ß = 2.671; se = 1.340; P = 0.046). In summary, the present work showed that metformin and gliclazide have a role in reducing BMD loss in patients with diabetes and are recommended for BMD loss prevention in diabetes.

Impact of habitual intake of glucosamine, fresh fruit, and tea on the risk of urolithiasis: A two-sample Mendelian randomization study.

Dietary patterns have a significant impact on the occurrence of urolithiasis. This study aimed to investigate the causal relationships between the consumption of glucosamine, fresh fruits, and tea, and the predisposition to urinary stones using a Mendelian randomization (MR) approach. Genetic proxies for these dietary factors were obtained from the UK Biobank, while the summary data for urolithiasis genome-wide association analyses were sourced from the FinnGen consortium. Five MR methodologies, namely inverse variance weighted (IVW), MR-Egger regression, weighted median, weighted mode, and simple mode, were employed in the analysis. To validate the findings, sensitivity evaluations such as the MR-PRESSO disruption test and Cochran Q test for heterogeneity were performed. The IVW method showed that glucosamine consumption had a strong inverse association with urolithiasis risk (Odds Ratio [OR] = 0.006, 95% Confidence Interval [CI] 0.0001-0.287, P = .009), surpassing the associations of fresh fruits (OR = 0.464, 95% CI 0.219-0.983, P = .045) and tea (OR = 0.550, 95% CI 0.345-0.878, P = .012). These findings were consistent when verified using alternative MR techniques, and the sensitivity analyses further supported their credibility. The results of this MR analysis demonstrate that regular consumption of glucosamine, fresh fruits, and tea is inversely correlated with the risk of developing urolithiasis.

No causal association between serum vitamin D levels and diabetes retinopathy: A Mendelian randomization analysis.

BACKGROUND AND AIM: Diabetes retinopathy (DR) is a common microvascular complication of diabetes, and it is the main cause of global vision loss. The current observational research results show that the causal relationship between Vitamin D and DR is still controversial. Therefore, we conducted a Mendelian randomization study to determine the potential causal relationship between serum 25-hydroxyvitamin D 25(OH)D and DR. METHODS AND RESULTS: In this study, we selected aggregated data on serum 25(OH)D levels (GWAS ID: ebi-a-GCST90000615) and DR (GWAS ID: finn-b-DM_RETINOPATHY) from a large-scale GWAS database. Then use MR analysis to evaluate the possible causal relationship between them. We mainly use inverse variance weighted (IVW), supplemented by MR Egger and weighted median methods. Sensitivity analysis is also used to ensure the stability of the results, such as Cochran's Q-test, MR-PRESSO, MR-Egger interception test, and retention method. The MR analysis results showed that there was no significant causal relationship between 25(OH)D and DR (OR = 1.0128, 95%CI=(0.9593,1.0693), P = 0.6447); Similarly, there was no significant causal relationship between DR and serum 25 (OH) D levels (OR = 0.9900, 95% CI=(0.9758,1.0045), P = 0.1771). CONCLUSION: Our study found no significant causal relationship between serum 25(OH)D levels and DR, and vice versa. A larger sample size randomized controlled trial is needed to further reveal its potential causal relationship.

Blood metabolites mediate the impact of lifestyle factors on the risk of urolithiasis: a multivariate, mediation Mendelian randomization study.

Urolithiasis is closely linked to lifestyle factors. However, the causal relationship and underlying mechanisms remain unclear. This study aims to investigate the relationship between lifestyle factors and the onset of urolithiasis and explore potential blood metabolite mediators and their role in mediating this relationship. In this study, we selected single nucleotide polymorphisms (SNPs) as instrumental variables if they exhibited significant associations with our exposures in genome-wide association studies (GWAS) (p < 5.0 × 10-8). Summary data for urolithiasis came from the FinnGen database, including 8597 cases and 333,128 controls. We employed multiple MR analysis methods to assess causal links between genetically predicted lifestyle factors and urolithiasis, as well as the mediating role of blood metabolites. A series of sensitivity and pleiotropy analyses were also conducted. Our results show that cigarettes smoked per day (odds ratio [OR] = 1.159, 95% confidence interval [CI] = 1.004-1.338, p = 0.044) and alcohol intake frequency (OR = 1.286, 95% CI = 1.056-1.565, p = 0.012) were positively associated with increased risk of urolithiasis, while tea intake (OR = 0.473, 95% CI = 0.299-0.784, p = 0.001) was positively associated with reduced risk of urolithiasis. Mediation analysis identifies blood metabolites capable of mediating the causal relationship between cigarettes smoked per day, tea intake and urolithiasis. We have come to the conclusion that blood metabolites serve as potential causal mediators of urolithiasis, underscoring the importance of early lifestyle interventions and metabolite monitoring in the prevention of urolithiasis.

Genome-wide Analysis Identified SEMA4D, Novel Candidate Gene for Temperature Sensitivity in Patients With Non-Small Cell Lung Cancer.

BACKGROUND: In the era of precision medicine, individual temperature sensitivity has been highlighted. This trait has traditionally been used for cold-heat pattern identification to understand the inherent physical characteristics, which are influenced by genetic factors, of an individual. However, genome-wide association studies (GWASs) on this trait are limited. METHODS: Using genotype data from 90 patients with advanced non-small cell lung cancer (NSCLC) and epidermal growth factor receptor mutations, we performed a GWAS to assess the association between single nucleotide polymorphisms (SNPs) and temperature sensitivity, such as cold and heat scores. The score of each participant was evaluated using self-administered questionnaires on common symptoms and a 15-item symptom-based cold-heat pattern identification questionnaire. RESULTS: The GWAS was adjusted for confounding factors, including age and sex, and significant associations were identified for cold and heat scores: SNP rs145814326, located on the intron of SORCS2 at chromosome 4p16.1, had a P-value of 1.86 × 10-7; and SNP rs79297667, located upstream from SEMA4D at chromosome 9q22.2, had a P-value of 8.97 × 10-8. We also found that the genetic variant regulates the expression level of SEMA4D in the main tissues, including the lungs and white blood cells, in NSCLC. CONCLUSIONS: SEMA4D was found to be significantly associated with temperature sensitivity in patients with NSCLC, suggesting an increased expression of SEMA4D in patients with higher heat scores. The potential role of temperature sensitivity as a prognostic or predictive marker of immune response in NSCLC should be further studied.

Associations of educational attainment with Sepsis mediated by metabolism traits and smoking: a Mendelian randomization study.

Objective: Sepsis constitutes a significant global healthcare burden. Studies suggest a correlation between educational attainment and the likelihood of developing sepsis. Our goal was to utilize Mendelian randomization (MR) in order to examine the causal connection between educational achievement (EA) and sepsis, while measuring the mediating impacts of adjustable variables. Methods: We collected statistical data summarizing educational achievement (EA), mediators, and sepsis from genome-wide association studies (GWAS). Employing a two-sample Mendelian randomization (MR) approach, we calculated the causal impact of education on sepsis. Following this, we performed multivariable MR analyses to assess the mediation proportions of various mediators, including body mass index (BMI), smoking, omega-3 fatty acids, and apolipoprotein A-I(ApoA-I). Results: Genetic prediction of 1-SD (4.2 years) increase in educational attainment (EA) was negatively correlated with sepsis risk (OR = 0.83, 95% CI 0.71 to 0.96). Among the four identified mediators, ranked proportionally, they including BMI (38.8%), smoking (36.5%), ApoA-I (6.3%) and omega-3 (3.7%). These findings remained robust across a variety of sensitivity analyses. Conclusion: The findings of this study provided evidence for the potential preventive impact of EA on sepsis, which may be influenced by factors including and metabolic traits and smoking. Enhancing interventions targeting these factors may contribute to reducing the burden of sepsis.

Genome-wide analyses of the GbAP2 subfamily reveal the function of GbTOE1a in salt and drought stress tolerance in Ginkgo biloba.

The APETALA2 (AP2) transcription factors play crucial roles in plant growth and stage transition. Ginkgo biloba is an important medicinal plant renowned for the rich flavonoid content in its leaves. In this study, 18 GbAP2s were identified from the G. biloba genome and classified into three clusters. We found that the members of the euAP2 cluster, including four TOEs (GbTOE1a/1b/1c/3), exhibited a higher expression level in most samples compared to other members. Specifically, GbTOE1a may have a positive regulatory role in salt and drought stress responses. The overexpression of GbTOE1a in G. biloba calli resulted in a significant increase in the flavonoid content and upregulation of flavonoid biosynthesis genes, including PAL, 4CL, CHS, F3H, FLSs, F3'Hs, OMT, and DFRs. By contrast, the silencing of GbTOE1a in seedlings decreased the flavonoid content and the expression of flavonoid synthesizing genes. In addition, the silenced seedlings exhibited decreased antioxidant levels and a higher sensitivity to salt and drought treatments, suggesting a crucial role of GbTOE1a in G. biloba salt and drought tolerance. To the best of our knowledge, this was the first investigation into the identification and characterization of GbAP2s in G. biloba. Our results lay a foundation for further research on the regulatory role of the AP2 family in flavonoid synthesis and stress responses.

Mental health and lower urinary tract symptoms: Results from the NHANES and Mendelian randomization study.

BACKGROUND: The clinical observations suggest a correlation between lower urinary tract symptoms (LUTSs) and mental health problems. Nonetheless, establishing a direct causal relationship between them remains challenging. METHODS: We initially conducted a cross-sectional study using 2005-2018 the National Health and Nutrition Examination Survey (NHANES) data. Multivariable-adjusted logistic regression was the primary statistical approach. Additionally, we employed Mendelian randomization (MR) to reducing confounding and reverse causation. Genetic instruments were obtained from publicly available genome-wide association study (GWAS) databases. Inverse Variance Weighted was the primary statistical method. RESULTS: The cross-sectional study involved 29,439 participants. Individuals with mental health problems had a higher risk of urinary incontinence (OR:4.38; 95%CI:3.32-5.76; P < 0.01) and overactive bladder (OR:2.31; 95%CI:2.02-2.63; P < 0.01). MR analysis then indicated a potential causal relationship between mental health problems and LUTSs. Depression symptoms was linked with urinary tract infection (UTI) (OR:1.005; 95%CI:1.003-1.008; PFDR < 0.01). Anxiety symptoms was related to the occurrence of UTI (OR:1.024; 95%CI:1.011-1.037; PFDR < 0.01) and bladder calcified/ contracted/ overactive (OR:1.017; 95%CI:1.007-1.027; PFDR < 0.01). The personality trait of neuroticism was related to the occurrence of cystitis (OR:1.072; 95%CI:1.022-1.125; PFDR = 0.02), extravasation of urine and difficulties with micturition (OR:1.001; 95%CI:1.001-1.002; PFDR < 0.01), and urinary frequency and incontinence (OR: 1.001; 95%CI:1.000-1.001; PFDR < 0.01). CONCLUSIONS: Our study provides various evidence for the correlation between mental health and LUTSs, emphasizing the significance of adopting a holistic approach to LUTSs management that incorporates both physical and psychological factors.

Elucidating the causal landscape: Mendelian randomization analysis of lifestyle and physiological factors in stress urinary incontinence.

PURPOSE: To explore the potential causal links between obesity, type 2 diabetes (T2D), and lifestyle choices (such as smoking, alcohol and coffee consumption, and vigorous physical activity) on stress urinary incontinence (SUI), this study employs a Mendelian Randomization approach. This research aims to clarify these associations, which have been suggested but not conclusively established in prior observational studies. METHODS: Genetic instruments associated with the exposures at the genome-wide significance (p < 5 × 10-8) were selected from corresponding genome-wide association studies. Summary-level data for SUI, was obtained from the UK Biobank. A two-sample MR analysis was employed to estimate causal effects, utilizing the inverse-variance weighted (IVW) method as the primary analytical approach. Complementary sensitivity analyses including MR-PRESSO, MR-Egger, and weighted median methods were performed. The horizontal pleiotropy was detected by using MR-Egger intercept and MR-PRESSO methods, and the heterogeneity was assessed using Cochran's Q statistics. RESULTS: Our findings demonstrate a significant causal relationship between higher body mass index (BMI) and the risk of SUI, with increased abdominal adiposity (WHRadjBMI) similarly linked to SUI. Smoking initiation is also causally associated with an elevated risk. However, our analysis did not find definitive causal connections for other factors, including T2D, alcohol consumption, coffee intake, and vigorous physical activity. CONCLUSIONS: These findings provide valuable insights for clinical strategies targeting SUI, suggesting a need for heightened awareness and potential intervention in individuals with higher BMI, WHR, and smoking habits. Further research is warranted to explore the complex interplay between genetic predisposition and lifestyle choices in the pathogenesis of SUI.

E3 ubiquitin ligase rififylin has yin and yang effects on rabbit cardiac transient outward potassium currents (Ito) and corresponding channel proteins.

Genome-wide association studies have reported a correlation between a SNP of the RING finger E3 ubiquitin protein ligase rififylin (RFFL) and QT interval variability in humans (Newton-Cheh et al., 2009). Previously, we have shown that RFFL downregulates expression and function of the human-like ether-a-go-go-related gene potassium channel and corresponding rapidly activating delayed rectifier potassium current (IKr) in adult rabbit ventricular cardiomyocytes. Here, we report that RFFL also affects the transient outward current (Ito), but in a peculiar way. RFFL overexpression in adult rabbit ventricular cardiomyocytes significantly decreases the contribution of its fast component (Ito,f) from 35% to 21% and increases the contribution of its slow component (Ito,s) from 65% to 79%. Since Ito,f in rabbits is mainly conducted by Kv4.3, we investigated the effect of RFFL on Kv4.3 expressed in HEK293A cells. We found that RFFL overexpression reduced Kv4.3 expression and corresponding Ito,f in a RING domain-dependent manner in the presence or absence of its accessory subunit Kv channel-interacting protein 2. On the other hand, RFFL overexpression in Kv1.4-expressing HEK cells leads to an increase in both Kv1.4 expression level and Ito,s, similarly in a RING domain-dependent manner. Our physiologically detailed rabbit ventricular myocyte computational model shows that these yin and yang effects of RFFL overexpression on Ito,f, and Ito,s affect phase 1 of the action potential waveform and slightly decrease its duration in addition to suppressing IKr. Thus, RFFL modifies cardiac repolarization reserve via ubiquitination of multiple proteins that differently affect various potassium channels and cardiac action potential duration.

Assessing the association between tea intake and risk of dental caries and periodontitis: a two-sample Mendelian randomization study.

Tea is an indispensable beverage in people's daily life. However, the relationship between tea intake and dental caries and periodontitis is controversial. We extracted datasets for tea intake and oral diseases from genome-wide association studies (GWASs) conducted by the UK Biobank and the Gene Lifestyle Interactions in Dental Endpoints consortium. We selected 38 single-nucleotide polymorphisms (SNPs) significantly associated with tea intake as instrumental variables (IVs) (P < 5.0 × 10-8). Mendelian randomization (MR) was performed to investigate the potential causality between tea intake and caries and periodontitis. Multivariable Mendelian randomization (MVMR) analyses were utilized to estimate causal effects of tea intake on risk of caries and periodontitis after adjusting for smoking, body mass index (BMI), and socioeconomic factors. The results showed that higher tea intake was suggestively associated with fewer natural teeth (ß = - 0.203; 95% CI = 0.680 to 0.980; P = 0.029) and higher risk of periodontitis (OR = 1.622; 95% CI = 1.194 to 2.205; P = 0.002). After Bonferroni correction, the causality of tea intake on periodontitis remained significant. The significance of periodontitis disappeared after adjusting for the socioeconomic factors in MVMR (OR = 1.603; 95% CI = 0.964 to 2.666; P = 0.069). Tea intake had no association with risk of caries. Statistical insignificance of the heterogeneity test and pleiotropy test supported the validity of the MR study. Our results provide insight into the potential relationship between tea intake and oral diseases from a dietary lifestyle perspective, which may help prevent oral diseases.

Genomic insight into the origin, domestication, dispersal, diversification and human selection of Tartary buckwheat.

BACKGROUND: Tartary buckwheat, Fagopyrum tataricum, is a pseudocereal crop with worldwide distribution and high nutritional value. However, the origin and domestication history of this crop remain to be elucidated. RESULTS: Here, by analyzing the population genomics of 567 accessions collected worldwide and reviewing historical documents, we find that Tartary buckwheat originated in the Himalayan region and then spread southwest possibly along with the migration of the Yi people, a minority in Southwestern China that has a long history of planting Tartary buckwheat. Along with the expansion of the Mongol Empire, Tartary buckwheat dispersed to Europe and ultimately to the rest of the world. The different natural growth environments resulted in adaptation, especially significant differences in salt tolerance between northern and southern Chinese Tartary buckwheat populations. By scanning for selective sweeps and using a genome-wide association study, we identify genes responsible for Tartary buckwheat domestication and differentiation, which we then experimentally validate. Comparative genomics and QTL analysis further shed light on the genetic foundation of the easily dehulled trait in a particular variety that was artificially selected by the Wa people, a minority group in Southwestern China known for cultivating Tartary buckwheat specifically for steaming as a staple food to prevent lysine deficiency. CONCLUSIONS: This study provides both comprehensive insights into the origin and domestication of, and a foundation for molecular breeding for, Tartary buckwheat.

Tea intake and lung diseases: a Mendelian randomization study.

Background: Existing 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 methods: We 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. Results: IVW 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. Conclusion: Our 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.

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.

BACKGROUND: Previous studies have emphasized the association between the intake of artificial sweeteners (AS) and type 2 diabetes mellitus (T2DM), but the causative relationship remains ambiguous. METHODS: This study employed univariate Mendelian randomization (MR) analysis to assess the causal link between AS intake from various sources and T2DM. Linkage disequilibrium score (LDSC) regression was used to evaluate the correlation between phenotypes. Multivariate and mediation MR were applied to investigate confounding factors and mediating effects. Data on AS intake from different sources (N = 64,949) were sourced from the UK Biobank, while T2DM data were derived from the DIAbetes Genetics Replication And Meta-analysis.The primary method adopted was inverse variance weighted (IVW), complemented by three validation techniques. Additionally, a series of sensitivity analyses were performed to evaluate pleiotropy and heterogeneity. RESULTS: LDSC analysis unveiled a significant genetic correlation between AS intake from different sources and T2DM (rg range: -0.006 to 0.15, all P < 0.05). After correction by the false discovery rate (FDR), the primary IVW method indicated that AS intake in coffee was a risk factor for T2DM (OR = 1.265, 95% CI: 1.035-1.545, P = 0.021, PFDR = 0.042). Further multivariable and mediation MR analyses pinpointed high density lipoprotein-cholesterol (HDL-C) as mediating a portion of this causal relationship. In reverse MR analysis, significant evidence suggested a positive correlation between T2DM and AS intake in coffee (ß = 0.013, 95% CI: 0.004-0.022, P = 0.004, PFDR = 0.012), cereal (ß = 0.007, 95% CI: 0.002-0.012, P = 0.004, PFDR = 0.012), and tea (ß = 0.009, 95% CI: 0.001-0.017, P = 0.036, PFDR = 0.049). No other causal associations were identified (P > 0.05, PFDR > 0.05). CONCLUSION: The MR analysis has established a causal relationship between AS intake in coffee and T2DM. The mediation by HDL-C emphasizes potential metabolic pathways underpinning these relationships.