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Frontiers in Immunology 2024Extensive research has been conducted on the correlation between adipose tissue and the risk of malignant lymphoma. Despite numerous observational studies exploring this...
BACKGROUND
Extensive research has been conducted on the correlation between adipose tissue and the risk of malignant lymphoma. Despite numerous observational studies exploring this connection, uncertainty remains regarding a causal relationship between adipose tissue and malignant lymphoma.
METHODS
The increase or decrease in adipose tissue was represented by the height of BMI. The BMI and malignant lymphoma genome-wide association studies (GWAS) used a summary dataset from the OPEN GWAS website. Single-nucleotide polymorphisms (SNPs) that met the criteria of P <5e-8 and LD of r= 0.001 in the BMI GWAS were chosen as genetic instrumental variants (IVs). Proxy SNPs with LD of r > 0.8 were identified, while palindromic and outlier SNPs were excluded. Mendelian randomization (MR) analysis used five methods, including inverse-variance weighted (IVW) model, weighted median (WM), MR-Egger, simple mode, and weighted mode. Sensitivity assessments included Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis. Participants randomly selected by the National Center for Health Statistics (NHANSE) and newly diagnosed HL patients at Fujian Medical University Union Hospital were used for external validation.
RESULTS
The results of the MR analysis strongly supported the causal link between BMI and Hodgkin's lymphoma (HL). The research demonstrated that individuals with lower BMI face a significantly increased risk of developing HL, with a 91.65% higher risk (OR = 0.0835, 95% CI 0.0147 - 0.4733, P = 0.005). No signs of horizontal or directional pleiotropy were observed in the MR studies. The validation results aligned with the results from the MR analysis (OR = 0.871, 95% CI 0.826 - 0.918, P< 0.001). And there was no causal relationship between BMI and non-Hodgkin's lymphoma (NHL).
CONCLUSIONS
The MR analysis study demonstrated a direct correlation between lower BMI and HL. This suggested that a decrease in adipose tissue increases the risk of developing HL. Nevertheless, further research is essential to grasp the underlying mechanism of this causal association comprehensively.
Topics: Humans; Mendelian Randomization Analysis; Hodgkin Disease; Adipose Tissue; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Body Mass Index; Genetic Predisposition to Disease; Female; Male; Risk Factors; Adult; Middle Aged
PubMed: 38873599
DOI: 10.3389/fimmu.2024.1400756 -
Food Science & Nutrition Jun 2024Meat intake, particularly from oily fish, has been associated with various chronic diseases. However, its relationship with acne has always been controversial....
Meat intake, particularly from oily fish, has been associated with various chronic diseases. However, its relationship with acne has always been controversial. Therefore, we have adopted Mendelian randomization (MR) analysis to investigate the causal relationship between different types of meat intake and acne. The exposure and outcome datasets for this study were obtained from the Integrative Epidemiology Unit (IEU) Open GWAS project. Seven datasets on meat intake were included, which consisted of non-oily fish, oily fish, lamb/mutton, poultry, pork, beef, and processed meat. The main methods used for MR analysis were inverse variance weighted, weighted median, and MR-egger. To ensure the accuracy of the results, heterogeneity, pleiotropy, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) analyses were conducted. Additionally, an analysis of four risk factors (fasting insulin, insulin resistance, total testosterone level, and estradiol level) was performed to investigate the underlying mechanisms linking statistically significant meat intake to acne. Oily fish intake was found to be a protective factor for acne (OR: 0.22, 95% CI: 0.10-0.49, < .001), and it was also observed that oily fish intake can reduce the level of fasting insulin by the IVW method (OR: 0.89, 95% CI: 0.81-0.98, = .02). No causal relationship was identified between other types of meat intake and acne. The intake of oily fish reduces the risk of acne by lowering fasting insulin levels.
PubMed: 38873457
DOI: 10.1002/fsn3.4054 -
Frontiers in Aging Neuroscience 2024Observational studies have reported inconsistent results on the relationship between chronic kidney disease (CKD) and age-related macular degeneration (AMD). The primary...
PURPOSE
Observational studies have reported inconsistent results on the relationship between chronic kidney disease (CKD) and age-related macular degeneration (AMD). The primary objective of this study was to investigate the causal relationships between estimated glomerular filtration rate (eGFR), CKD, its common causes, and AMD among participants of European descent.
METHODS
Genetic variants associated with eGFR, CKD and its common causes, encompassing diabetic nephropathy (DN), immunoglobulin A nephropathy (IgAN), and membranous nephropathy (MN) were obtained from previously published genome-wide association studies (GWAS) and FinnGen database. Summary statistics for early AMD, AMD, dry AMD, and wet AMD were acquired from the GWAS and FinnGen database. Inverse-variance-weighted (IVW) method was the main MR analysis. Sensitivity analyses were performed with Cochran's Q, MR-Egger intercept, and leave-one-out analysis. In addition, RadialMR was utilized to identify and remove outliers.
RESULTS
IVW results showed that CKD, eGFR were not associated with any type of AMD ( > 0.05). DN (OR: 1.042, 95% CI: 1.002-1.083, = 0.037) and MN (OR: 1.023, 95% CI: 1.007-1.040, = 0.005) were associated with an increased risk of earl AMD. DN (OR: 1.111, 95% CI: 1.07-1.154, = 4.87 × 10), IgAN (OR: 1.373, 95% CI: 1.097-1.719, = 0.006), and MN (OR: 1.036, 95% CI: 1.008-1.064, = 0.012) were associated with an increased risk of AMD. DN (OR: 1.090, 95% CI: 1.042-1.140, = 1.57 × 10) and IgAN (OR: 1.480, 95% CI: 1.178-1.858, = 7.55 × 10) were associated with an increased risk of dry AMD. The risk of wet AMD was associated with DN (OR: 1.107, 95% CI: 1.043-1.174, = 7.56 × 10) and MN (OR: 1.071, 95% CI: 1.040-1.103, = 5.48 × 10).
CONCLUSION
This MR study found no evidence of causal relationship between CKD and AMD. DN, IgAN, and MN may increase risk of AMD. This findings underscore the importance of ocular examinations in patients with DN, MN, and IgAN. More studies are needed to support the findings of our current study.
PubMed: 38872627
DOI: 10.3389/fnagi.2024.1399666 -
HGG Advances Jun 2024The high heritability of amyotrophic lateral sclerosis (ALS) contrasts with its low molecular diagnosis rate post-genetic testing, pointing to potential undiscovered...
The high heritability of amyotrophic lateral sclerosis (ALS) contrasts with its low molecular diagnosis rate post-genetic testing, pointing to potential undiscovered genetic factors. To aid the exploration of these factors, we introduced EpiOut, an algorithm to identify chromatin accessibility outliers that are regions exhibiting divergent accessibility from the population baseline in a single or few samples. Annotation of accessible regions with histone chromatin immunoprecipitation sequencing and Hi-C indicates that outliers are concentrated in functional loci, especially among promoters interacting with active enhancers. Across different omics levels, outliers are robustly replicated, and chromatin accessibility outliers are reliable predictors of gene expression outliers and aberrant protein levels. When promoter accessibility does not align with gene expression, our results indicate that molecular aberrations are more likely to be linked to post-transcriptional regulation rather than transcriptional regulation. Our findings demonstrate that the outlier detection paradigm can uncover dysregulated regions in rare diseases. EpiOut is available at github.com/uci-cbcl/EpiOut.
PubMed: 38872308
DOI: 10.1016/j.xhgg.2024.100318 -
Scientific Reports Jun 2024Fair allocation of funding in multi-centre clinical studies is challenging. Models commonly used in Germany - the case fees ("fixed-rate model", FRM) and up-front...
Fair allocation of funding in multi-centre clinical studies is challenging. Models commonly used in Germany - the case fees ("fixed-rate model", FRM) and up-front staffing and consumables ("up-front allocation model", UFAM) lack transparency and fail to suitably accommodate variations in centre performance. We developed a performance-based reimbursement model (PBRM) with automated calculation of conducted activities and applied it to the cohorts of the National Pandemic Cohort Network (NAPKON) within the Network of University Medicine (NUM). The study protocol activities, which were derived from data management systems, underwent validation through standardized quality checks by multiple stakeholders. The PBRM output (first funding period) was compared among centres and cohorts, and the cost-efficiency of the models was evaluated. Cases per centre varied from one to 164. The mean case reimbursement differed among the cohorts (1173.21€ [95% CI 645.68-1700.73] to 3863.43€ [95% CI 1468.89-6257.96]) and centres and mostly fell short of the expected amount. Model comparisons revealed higher cost-efficiency of the PBRM compared to FRM and UFAM, especially for low recruitment outliers. In conclusion, we have developed a reimbursement model that is transparent, accurate, and flexible. In multi-centre collaborations where heterogeneity between centres is expected, a PBRM could be used as a model to address performance discrepancies.Trial registration: https://clinicaltrials.gov/ct2/show/NCT04768998 ; https://clinicaltrials.gov/ct2/show/NCT04747366 ; https://clinicaltrials.gov/ct2/show/NCT04679584 .
Topics: Humans; Germany; Cost-Benefit Analysis; Reimbursement Mechanisms; Cohort Studies; COVID-19
PubMed: 38871878
DOI: 10.1038/s41598-024-63945-5 -
PloS One 2024Previous research has underscored the correlation between Alzheimer's disease (AD) and erectile dysfunction (ED). However, due to inherent limitations of observational...
BACKGROUND
Previous research has underscored the correlation between Alzheimer's disease (AD) and erectile dysfunction (ED). However, due to inherent limitations of observational studies, the causative relationship remains inconclusive.
METHODS
Utilizing publicly available data from genome-wide association studies (GWAS) summary statistics, this study probed the potential causal association between AD and ED using univariate Mendelian randomization (MR). Further, the multivariable MR assessed the confounding effects of six cardiovascular diseases (CVDs). The primary approach employed was inverse variance weighted (IVW), supplemented by three additional methods. A series of sensitivity analyses were conducted to ensure the robustness of the results.
RESULTS
In the forward MR analysis, the IVW method revealed causal evidence of genetically predicted AD being a risk factor for ED (OR = 1.077, 95% CI 1.007∼1.152, P = 0.031). Reverse analysis did not demonstrate any causal evidence linking ED to AD (OR = 1.018, 95% CI 0.974∼1.063, P = 0.430). Multivariable MR analysis showed that after adjusting for coronary heart disease (OR = 1.082, 95% CI 0.009∼1.160, P = 0.027), myocardial infarction (OR = 1.085, 95% CI 1.012∼1.163, P = 0.022), atrial fibrillation (OR = 1.076, 95% CI 1.002∼1.154, P = 0.043), heart failure (OR = 1.103, 95% CI 1.024∼1.188, P = 0.010), ischemic stroke (OR = 1.079, 95% CI 1.009∼1.154, P = 0.027), hypertension (OR = 1.092, 95% CI 1.011∼1.180, P = 0.025), and all models (OR = 1.115, 95% CI 1.024∼1.214, P = 0.012), the causal association between AD and ED persisted. Sensitivity analyses confirmed the absence of pleiotropy, heterogeneity, and outliers, validating the robustness of our results (P > 0.05).
CONCLUSIONS
This MR study consistently evidences a causal effect of genetically predicted AD on the risk of ED, independent of certain CVDs, yet offers no evidence for a reverse effect from ED.
Topics: Humans; Male; Alzheimer Disease; Erectile Dysfunction; Mendelian Randomization Analysis; Cardiovascular Diseases; Genome-Wide Association Study; Risk Factors; Polymorphism, Single Nucleotide
PubMed: 38870203
DOI: 10.1371/journal.pone.0303338 -
Scientific Reports Jun 2024In real-life situations, we have to analyze the data that contains the atypical observations, and the presence of outliers has adverse effects on the performance of...
In real-life situations, we have to analyze the data that contains the atypical observations, and the presence of outliers has adverse effects on the performance of ordinary least square estimates. In this situation, redescedning M-estimators, proposed by Huber (1964), are used to tackle the effects of outliers to increase the efficiency of least square estimates. In this study, we introduce a redescending M-estimator designed to generate robust estimates by mitigating the influence of outlier observations, even when the tuning constant is set to low values. This innovative estimator exhibits enhanced linearity at its core and maintains continuity throughout its range. Our proposed estimator stands out for its novelty, simplicity, differentiability, and practical applicability across real-world scenarios. The results of the proposed redescedning M-estimators are compared with existing robust estimators using an extensive simulation study. Two examples based on real-life data are also added to validate the performance of the suggested function. The formulated redescedning M-estimator produced efficient results as compared to all the considered redescedning M-estimators.
PubMed: 38866829
DOI: 10.1038/s41598-024-64239-6 -
Scientific Reports Jun 2024The growing application of carbon dioxide (CO) in various environmental and energy fields, including carbon capture and storage (CCS) and several CO-based enhanced oil...
The growing application of carbon dioxide (CO) in various environmental and energy fields, including carbon capture and storage (CCS) and several CO-based enhanced oil recovery (EOR) techniques, highlights the importance of studying the phase equilibria of this gas with water. Therefore, accurate prediction of CO solubility in water becomes an important thermodynamic property. This study focused on developing two powerful intelligent models, namely gradient boosting (GBoost) and light gradient boosting machine (LightGBM) that predict CO solubility in water with high accuracy. The results revealed the outperformance of the GBoost model with root mean square error (RMSE) and determination coefficient (R) of 0.137 mol/kg and 0.9976, respectively. The trend analysis demonstrated that the developed models were highly capable of detecting the physical trend of CO solubility in water across various pressure and temperature ranges. Moreover, the Leverage technique was employed to identify suspected data points as well as the applicability domain of the proposed models. The results showed that less than 5% of the data points were detected as outliers representing the large applicability domain of intelligent models. The outcome of this research provided insight into the potential of intelligent models in predicting solubility of CO in pure water.
PubMed: 38866817
DOI: 10.1038/s41598-024-63159-9 -
The Science of the Total Environment Sep 2024West Nile (WNV) is a zoonotic arbovirus with an expanding geographical range and epidemic activity in Europe. Not having yet experienced a human-associated epidemic,...
West Nile (WNV) is a zoonotic arbovirus with an expanding geographical range and epidemic activity in Europe. Not having yet experienced a human-associated epidemic, Portugal remains an outlier in the Mediterranean basin. In this study, we apply ecological niche modelling informed by WNV historical evidence and a multitude of environmental variables from across Portugal. We identify that ecological backgrounds compatible with WNV historical circulation are mostly restricted to the south, characterized by a warmer and drier climate, high avian diversity, specific avian species and land types. We estimate WNV ecological suitability across the country, identifying overlaps with the distributions of the three relevant hosts (humans, birds, equines) for public and animal health. From this, we propose a category-based spatial framework providing first of a kind valuable insights for WNV surveillance in Portugal under the One Health nexus. We forecast that near future climate trends alone will contribute to pushing adequate WNV ecological suitability northwards, towards regions with higher human density. This unique perspective on the past, present and future ecology of WNV addresses existing national knowledge gaps, enhances our understanding of the evolving emergence of WNV, and offers opportunities to prepare and respond to the first human-associated epidemic in Portugal.
Topics: Portugal; West Nile Fever; West Nile virus; Animals; Humans; Birds; One Health; Ecosystem; Horses
PubMed: 38866158
DOI: 10.1016/j.scitotenv.2024.173875 -
Frontiers in Microbiology 2024Osteomyelitis is characterized by an inflammatory process initiated by microorganisms, leading to infection and subsequent degradation of bone tissue. Several studies...
BACKGROUND
Osteomyelitis is characterized by an inflammatory process initiated by microorganisms, leading to infection and subsequent degradation of bone tissue. Several studies have indicated a potential link between gut microbiota and the occurrence of osteomyelitis. Utilizing the benefits of Mendelian randomization, which mitigates issues of confounding and reverse causation, we employed this approach to ascertain the presence of a causal connection between gut microbiota and osteomyelitis. Additionally, we aimed to pinpoint gut microbiota that could potentially exert substantial influence.
METHODS
We performed a rigorous screening of single nucleotide polymorphisms in GWAS summary statistics for gut microbiota and osteomyelitis. The 2,542 instrumental variables obtained after screening were subjected to MR analyses, including inverse variance weighting, weighted median, weighted mode, MR-Egger, and Mendelian randomization pleiotropy residual sum and outlier test. We then validated the reliability of the results by performing sensitivity analyses on the MR of 196 well-defined gut microbiota.
RESULT
We established a causal relationship between gut microbiota and osteomyelitis through MR analysis. Additionally, we identified a taxon of significant importance and six taxons with nominal significance. Specifically, the family Bacteroidales S24.7 group exhibited an association with a diminished risk of osteomyelitis development. Conversely, the class Bacilli, class Bacteroidia, order Bacteroidales, order Lactobacillales, family Streptococcaceae, and genus Coprococcus3 displayed an increased risk of developing osteomyelitis. The MR outcomes for these seven taxa remained stable throughout a series of sensitivity analyses.
CONCLUSION
This study demonstrated a causal relationship between gut microbiota and osteomyelitis by Mendelian randomization. We hope that this study will provide a new direction for the treatment of osteomyelitis, which has a paucity of therapeutic options.
PubMed: 38863758
DOI: 10.3389/fmicb.2024.1342172