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BACKGROUND: Numerous research works have investigated the association between tea consumption and the risk of acute cerebrovascular events; however, the results are inconsistent. OBJECTIVES: We used Mendelian randomization (MR) to evaluate the causal association between tea intake and several acute cerebrovascular events, including any ischemic stroke, large atherosclerotic stroke (LAS), cardiogenic embolic stroke (CES), small vessel stroke (SVS), intracranial hemorrhage (ICH), and subarachnoid hemorrhage (SAH). METHODS: We obtained summary genome-wide association study (GWAS) data on tea intake and acute cerebrovascular events in populations of European ancestry. The GWAS on tea intake is derived from the UK Biobank, where we have chosen single-nucleotide polymorphisms (SNPs) closely associated with it as instrumental variables. We also obtained summary data on ischemic stroke from a GWAS meta-analysis, as well as summary data on ICH and SAH from the FinnGen study. We first explored the causal association between tea intake and several acute cerebrovascular events using univariate Mendelian randomization (UVMR), and then further assessed the causal association between tea intake and SVS using multivariate Mendelian randomization (MVMR) corrected for multiple confounders. RESULTS: In UVMR, genetically predicted increases in tea intake were linked to a lower risk of SVS (OR: 0.58; 95% CI: 0.39, 0.86). There was no causal association between tea intake and the risk of other acute cerebrovascular events. In the MVMR, our results show that there was still a significant causal association between drinking tea and SVS, after adjusting body mass index, total cholesterol, low-density lipoprotein cholesterol, diabetes, hypertension, smoking, and alcohol consumption. CONCLUSION: This MR study provides new genetic evidence that increased tea intake reduces the risk of SVS in the European population. However, possibly because of limited statistical power, the study did not find that tea consumption reduced the risk of several other acute cerebrovascular events.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Estudio de Asociación del Genoma Completo , Accidente Cerebrovascular/genética , LDL-Colesterol , Polimorfismo de Nucleótido Simple , Té , Análisis de la Aleatorización Mendeliana , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Alzheimer's disease (AD) is a degenerative disease of the nervous system. Observational studies have found an association between plant food intake and AD. However, it is unclear whether this association is influenced by confounding factors. We aimed to explore the causal relationship between plant-based diet and the risk of AD using two-sample Mendelian randomization. MATERIALS AND METHODS: We obtained datasets of exposure from the IEU Open GWAS project, including dried fruit intake, fresh fruit intake, raw vegetable intake, cooked vegetable intake, and cereal intake. The summary data for AD were obtained from a large GWAS meta-analysis containing 71,880 cases and 383,378 controls. RESULTS: Increased intake of dried fruits was associated with a reduced risk of AD (IVW: OR = 0.88, 95CI = 0.82-0.95). No causal association was found between the intake of other foods and AD. CONCLUSION: This MR study suggests that genetically predicted increased intake of dried fruits is a causal protective factor for AD.
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PURPOSE: Previous epidemiological and other studies have shown an association between diet and low back pain (LBP). This study aimed to investigate the causal relationship between diet and LBP using a Mendelian randomization (MR) approach. METHODS: The three main methods in this study were weighted median, MR-Egger, and inverse variance weighting (IVW). We utilized MR-PRESSO to eliminate abnormal SNPs. Additionally, tests for pleiotropy and heterogeneity were conducted. Utilizing IVW and MR-Egger's Cochran's Q test, heterogeneity was evaluated. MR-Egger intercepts were used in pleiotropy tests. A leave-one-out analysis was also used to evaluate the stability of the study's findings. RESULTS: The frequency of alcohol intake was associated with an increased risk of LBP. Increased processed meat intake, dried fruit intake, cereal intake, and tea intake were causally associated with a decreased risk of LBP (alcohol intake frequency: odds ratio (OR) = 1.28; 95% confidence interval (CI), 1.11-1.47; P = 0.0006; processed meat intake: OR = 0.60, 95%CI 0.39-0.92, P = 0.019; dried fruit intake: OR = 0.43, 95%CI 0.29-0.66, P = 0.00008; cereal intake: OR = 0.62, 95%CI 0.42-0.92, P = 0.018; tea intake: OR = 0.75, 95%CI 0.58-0.97, P = 0.029). Heterogeneity and pleiotropy were also not found in the sensitivity analysis. The leave-one-out analysis also showed more robust results. Other dietary intakes were not causally associated with LBP. CONCLUSIONS: This two-sample MR study found that frequency of alcohol intake was associated with an increased risk of LBP, and intake of processed meat, dried fruit, cereals, and tea was associated with a decreased risk of LBP. Moreover, no causal relationship was found with LBP in the other 13 diets.
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Dolor de la Región Lumbar , Análisis de la Aleatorización Mendeliana , Humanos , Dolor de la Región Lumbar/etiología , Dolor de la Región Lumbar/genética , Dieta/efectos adversos , Nonoxinol , TéRESUMEN
BACKGROUND: The association between hypothyroidism and stroke remains controversial and the association between hypothyroidism and stroke subtypes has not been satisfactorily researched. This study aimed to explore the causal effect of hypothyroidism on the risk of stroke and its subtypes by Mendelian randomization (MR) analysis. METHODS: Single nucleotide polymorphisms (SNPs) were selected from published genome-wide association studies (GWAS) meta-analysis as instrumental variables (IVs) for hypothyroidism. As outcomes, summary GWAS data for stroke and its subtypes were obtained from two other large GWAS meta-analyses, including any stroke (AS), any ischemic stroke (AIS), large vessel stroke (LAS), cardiogenic embolic stroke (CES), small vessel stroke (SVS), and intracranial hemorrhage (ICH). Univariate Mendelian randomization (UVMR) and multivariate Mendelian randomization (MVMR) were used to assess the causal effect of hypothyroidism on stroke and its subtypes. RESULTS: In UVMR, genetically predicted hypothyroidism was significantly associated with LAS (OR = 1.14, 95CI = 1.02-1.27) and SVS (OR = 1.14, 95CI = 1.04-1.25), but not with AS, AIS, CES, and ICH. The results of the MVMR showed that after adjusting for smoking, alcohol consumption, hypertension, diabetes, low-density lipoprotein cholesterol (LDL-c), and body mass index (BMI), the causal association between hypothyroidism and SVS remained significant, while the association between hypothyroidism and LAS became nonsignificant. CONCLUSION: Hypothyroidism is causally associated with risk for LAS and SVS, but not for other stroke subtypes. Hypothyroidism may be an independent risk factor for SVS, and vascular risk factors play an important role in hypothyroidism causing LAS.
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Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Hipotiroidismo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Accidente Cerebrovascular , Humanos , Hipotiroidismo/genética , Hipotiroidismo/epidemiología , Hipotiroidismo/diagnóstico , Factores de Riesgo , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Medición de Riesgo , Fenotipo , Accidente Cerebrovascular Isquémico/genética , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/epidemiología , Femenino , Accidente Cerebrovascular Embólico/genética , Accidente Cerebrovascular Embólico/etiología , Accidente Cerebrovascular Embólico/diagnóstico , Accidente Cerebrovascular Embólico/epidemiología , MasculinoRESUMEN
Viscosity is a typical physical parameter and plays an important role in nutrient transferring, diffusion process regulating and safety warning. Aberrant mitochondrial viscosity is closely associated with an imbalance in a liquid system. Nevertheless, there is currently a lack of convenient and efficient tools for the mutation of viscosity detection at the molecular level. Herein, a natural product xanthohumol (XTH) was extracted from Humulus lupulus and used to measure the microenvironmental viscosity. Due to the existence of carbonyl and phenolic hydroxyl groups, a typical twisted intramolecular charge transfer (TICT) was formed. The conjugated single and double bonds can be employed as the rotatable site. Consequently, a turn-on method based on viscosity response is developed. High sensitivity (x = 0.56) with a remarkable enhancement (55-fold) toward viscosity and a visualized fluorescent signal can be found. In addition, it displays a single selectivity with excellent photostability and pH stability in the complex liquid system. Using the extracted XTH, a typical application toward the liquid spoilage process was performed and a positive correlation was noted. Given the comprehensive properties of XTH, liquid safety inspection at a molecular level with natural source-extracted products can be obtained.
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BACKGROUND: Knee osteoarthritis (KOA) is a common disabling joint disease that affects millions of people worldwide. Diet may play a role in the etiology and progression of KOA, but evidence for a causal relationship is limited. We aimed to investigate the causal impact of dietary intake on KOA risk using Mendelian randomization (MR). METHODS: We used summary-level data from genome-wide association studies (GWAS) including dietary intake (n = 335, 394-462, 342), and KOA (n = 403, 124). We selected 6-77 genetic variants as instrumental variables for 18 dietary factors, including processed meat, poultry, beef, oily fish, non-oily fish, pork, lamb, frequency of alcohol intake, alcoholic beverages, tea, coffee, dried fruit, cereals, cheese, bread, cooked vegetables, salad/raw vegetables, and fresh fruit. We performed univariate and multivariate MR analyses to estimate the causal effect of each dietary factor on KOA risk. We also performed some sensitivity analyses to assess the validity of the MR hypothesis. RESULTS: We found that higher coffee intake was associated with increased KOA risk, whereas higher intake of dried fruits, grains, cheese, and oily fish was associated with reduced KOA risk. After multivariate adjustment, we found that coffee and oily fish intake may affect KOA through obesity, body mass index (BMI), diabetes, hypertension, and prolonged standing. Sensitivity analyses did not reveal any evidence of pleiotropy. CONCLUSIONS: Our study provides new causal evidence that dietary intake may influence KOA risk. Specifically, we suggest that increased intake of dried fruits, grains, cheese, and oily fish and decreased coffee intake may be beneficial in preventing and mitigating KOA. further studies are needed to elucidate the underlying mechanisms and to confirm our findings in different populations.
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Osteoartritis de la Rodilla , Bovinos , Humanos , Animales , Ovinos , Osteoartritis de la Rodilla/etiología , Osteoartritis de la Rodilla/genética , Análisis de la Aleatorización Mendeliana , Café , Estudio de Asociación del Genoma Completo , DietaRESUMEN
Objective: The causal relationship between Rheumatoid arthritis (RA) and hypothyroidism/hyperthyroidism remains controversial due to the limitations of conventional observational research, such as confounding variables and reverse causality. We aimed to examine the potential causal relationship between RA and hypothyroidism/hyperthyroidism using Mendelian randomization (MR). Method: We conducted a bidirectional two-sample univariable analysis to investigate the potential causal relationship between hypothyroidism/hyperthyroidism and RA. Furthermore, we performed a multivariate analysis to account for the impact of body mass index (BMI), smoking quantity, and alcohol intake frequency. Results: The univariable analysis indicated that RA has a causative influence on hypothyroidism (odds ratio [OR]=1.07, 95% confidence interval [CI]=1.01-1.14, P=0.02) and hyperthyroidism (OR=1.32, 95% CI=1.15-1.52, P<0.001). When hypothyroidism/hyperthyroidism was considered as an exposure variable, we only observed a causal relationship between hypothyroidism (OR=1.21, 95% CI=1.05-1.40, P=0.01) and RA, whereas no such connection was found between hyperthyroidism (OR=0.91, 95% CI=0.83-1.01, P=0.07) and RA. In the multivariate MR analyses, after separately and jointly adjusting for the effects of daily smoking quantity, alcohol intake frequency, and BMI, the causal impact of RA on hypothyroidism/hyperthyroidism and hypothyroidism on RA remained robust. However, there is no evidence to suggest a causal effect of hyperthyroidism on the risk of RA (P >0.05). Conclusion: Univariate and multivariate MR analyses have validated the causal association between RA and hypothyroidism/hyperthyroidism. Hypothyroidism confirmed a causal relationship with RA when employed as an exposure variable, whereas no such relationship was found between hyperthyroidism and RA.
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Artritis Reumatoide , Hipertiroidismo , Hipotiroidismo , Humanos , Análisis de la Aleatorización Mendeliana , Hipertiroidismo/complicaciones , Hipertiroidismo/genética , Hipotiroidismo/complicaciones , Artritis Reumatoide/complicaciones , Artritis Reumatoide/genética , Consumo de Bebidas Alcohólicas/efectos adversosRESUMEN
Objective: Investigating the association between inflammatory cytokines and hypothyroidism remains challenging due to limitations in traditional observational studies. In this study, we employed Mendelian randomization (MR) to assess the causal relationship between 41 inflammatory cytokines and hypothyroidism. Method: Inflammatory cytokines in 30,155 individuals of European ancestry with hypothyroidism and in a GWAS summary containing 8,293 healthy participants were included in the study for bidirectional two-sample MR analysis. We utilized inverse variance weighting (IVW), weighted median (WM), and Mendelian randomization-Egger (MR-Egger) methods. Multiple sensitivity analyses, including MR-Egger intercept test, leave-one-out analysis, funnel plot, scatterplot, and MR-PRESSO, were applied to evaluate assumptions. Results: We found evidence of a causal effect of IL-7 and macrophage inflammatory protein-1ß (MIP-1ß) on the risk of hypothyroidism, and a causal effect of hypothyroidism on several cytokines, including granulocyte colony-stimulating factor (G-CSF), IL-13, IL-16, IL-2rα, IL-6, IL-7, IL-9, interferon-γ-inducible protein 10 (IP10), monokine induced by interferon (IFN)-γ (MIG), macrophage inflammatory protein-1ß (MIP-1ß), stem cell growth factors-ß (SCGF-ß), stromal cell derived factor-1α (SDF-1α), and tumor necrosis factor-α (TNF-α). Conclusion: Our study suggests that IL-7 and MIP-1ß may play a role in the pathogenesis of hypothyroidism, and that hypothyroidism may induce a systemic inflammatory response involving multiple cytokines. These findings may have implications for the prevention and treatment of hypothyroidism and its complications. However, further experimental studies are needed to validate the causal relationships and the potential of these cytokines as drug targets.
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Citocinas , Hipotiroidismo , Humanos , Quimiocina CCL4 , Interleucina-7 , Análisis de la Aleatorización Mendeliana , Hipotiroidismo/genéticaRESUMEN
Background: Previous epidemiological and other studies have shown an association between ischemic stroke (IS) and frozen shoulder (FS). However, the causal relationship between them remains unclear. Therefore, the present study aimed to investigate the causal relationship between IS and FS using a two-sample Mendelian randomization method. Methods: Our research was divided into two stages: discovery and replication. The data were extracted from publicly available genome-wide association studies (GWAS). We selected a large sample of IS (n = 440, 328) and its subtypes (large-artery atherosclerotic stroke (LAS), cardioembolic stroke (CES), and stroke caused by small-vessel disease (SVS) and lacunar stroke (n = 254, 959) as exposure data. Additionally, we selected a large sample of FS as outcome data (n = 451, 099). Inverse variance weighting (IVW) was applied as the primary analysis method. The weighted median, MR-Egger, simple model, and weighted model were used as complementary analysis methods to assess causal effects. Moreover, heterogeneity was analyzed using Cochran's Q-test with IVW and MR-Egger. The MR-Egger intercept and MR-PRESSO analysis methods were used for pleiotropy testing. The stability of the results was also assessed using a leave-one-out analysis. Results: In the discovery stage, the IVW approach revealed an odds ratio (OR) of 1.207 with a 95% confidence interval (CI) of 1.027-1.417 and a P-value of 0.022. This suggests a causal association between IS levels and an increased risk of FS. In the subtype studies of IS, the findings were negative. However, during the replication stage, a significant causal link was found between selected lacunar strokes and FS with an OR of 1.252, a 95% CI of 1.105-1.419, and a P-value of 0.0004. All studies had no pleiotropy or heterogeneity, and the findings were robust. Conclusions: Our study confirmed the causal relationship between any IS level and increased risk of FS. Furthermore, the same results were obtained in the replication stage with lacunar stroke as an exposure factor. However, there was no direct causal relationship between the subtypes of IS and FS. Our study provides theoretical support for shoulder care for patients with IS.