Identifying genetic overlaps in obesity and metabolic disorders unlocking unique and shared mechanistic insights.

Objective: Obesity has a high heritability and frequently co-occurs with metabolic disorders, indicating shared genetic susceptibility. The underlying causative genes and biological mechanisms of obesity and metabolic disorders remain predominantly elusive.

Methods: The FinnGen R11 dataset, including over 450,000 subjects, was employed in conjunction with the Genotype-Tissue Expression Project (GTEx) v8 eQTls dataset to conduct cross-tissue transcriptome association studies, Functional Summary-based Imputation in single tissues, and Gene Analysis combined with Multimarker Analysis of Genomic Annotation, respectively, for identifying distinct and shared genetic architectures of obesity and metabolic disorders.

Pesticides have negative effects on non-target organisms.

Pesticides affect a diverse range of non-target species and may be linked to global biodiversity loss. The magnitude of this hazard remains only partially understood. We present a synthesis of pesticide (insecticide, herbicide and fungicide) impacts on multiple non-target organisms across trophic levels based on 20,212 effect sizes from 1,705 studies.

Role of Inflammatory Biomarkers in Mediating Causal Effect of Life Course Body Composition on Hypertension.

Background: The mediating role of inflammatory biomarkers in the causal relationship between body composition and hypertension remains unclear and requires further investigation.

Methods: This study used a combination of retrospective observational analysis and Mendelian randomization approaches. Observational data were derived from 4717 Chinese children and adolescents aged 6 to 18 years who underwent dual-energy X-ray absorptiometry to assess body composition.

Insights Into Causal Effects of Genetically Proxied Lipids and Lipid-Modifying Drug Targets on Cardiometabolic Diseases.

Background: The differential impact of serum lipids and their targets for lipid modification on cardiometabolic disease risk is debated. This study used Mendelian randomization to investigate the causal relationships and underlying mechanisms.

Methods: Genetic variants related to lipid profiles and targets for lipid modification were sourced from the Global Lipids Genetics Consortium.

Effect of life course body composition on lipids and coronary atherosclerosis mediated by inflammatory biomarkers.

Objective: To investigate the mediating role of inflammatory biomarkers in the causal effect of body composition on lipids and atherosclerosis.

Methods: Retrospective observational study and Mendelian randomization (MR) study were used. Observational analyses were undertaken using data from 4717 children and adolescents aged 6-18 years from Chinese who underwent dual-energy x-ray absorptiometry for body composition.

Mediating role of inflammatory biomarkers in the causal effect of body composition on glycaemic traits and type 2 diabetes.

Objective: The aim was to investigate the mediating role of inflammatory biomarkers in the causal effect of body composition on glycaemic traits and type 2 diabetes.

Methods: A retrospective observational study and a Mendelian randomization (MR) study were used. Observational analyses were performed using data from 4717 Chinese children and adolescents aged 6-18 years who underwent dual-energy X-ray absorptiometry for body composition.

Genetically proxied vitamin B12 and homocysteine in relation to life course adiposity and body composition.

Objective: Observational studies explore the association between vitamin B12 and obesity. However, causality is not reflected by such observations. We performed a bi-directional Mendelian randomization (MR) study to elucidate the causal relationship of vitamin B12 and homocysteine (Hcy) with life course adiposity and body composition.

Identification of a coagulation-related signature correlated with immune infiltration and their prognostic implications in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a fatal form of lung cancer with a poor prognosis. Coagulation system had been confirmed closely related to tumor progression and the hypercoagulable state encouraged the immune infiltration and development of tumor cells, leading to a poor prognosis in cancer patients. However, the use of the coagulation-related genes (CRGs) for prognosis in LUAD has yet to be determined.

Bi-directional causal effect between vitamin B12 and non-alcoholic fatty liver disease: Inferring from large population data.

Objectives: Many observational studies evaluate the association between vitamin B12 and non-alcoholic fatty liver disease (NAFLD). However, the causality of this association remains uncertain, especially in European populations. We conducted a bidirectional Mendelian randomization study to explore the association between vitamin B12 and NAFLD.

Inferring causal effects of homocysteine and B-vitamin concentrations on bone mineral density and fractures: Mendelian randomization analyses.

Objectives: In the progress of bone metabolism, homocysteine (Hcy) and B vitamins play substantial roles. However, the causal associations of homocysteine, B-vitamin concentrations with bone mineral density (BMD), and fractures remain unclear. Therefore, we employed a two-sample Mendelian randomization (MR) design to infer the causal effects of Hcy and B vitamins on BMD and fractures.

Causal effects of B vitamins and homocysteine on obesity and musculoskeletal diseases: A Mendelian randomization study.

Objectives: Although homocysteine (Hcy) increases the risk of cardiovascular diseases, its effects on obesity and musculoskeletal diseases remain unclear. We performed a Mendelian randomization study to estimate the associations between Hcy and B vitamin concentrations and their effects on obesity and musculoskeletal-relevant diseases in the general population.

Methods: We selected independent single nucleotide polymorphisms of Hcy ( = 44,147), vitamin B12 ( = 45,576), vitamin B6 ( = 1864), and folate ( = 37,465) at the genome-wide significance level as instruments and applied them to the studies of summary-level data for fat and musculoskeletal phenotypes from the UK Biobank study ( = 331,117), the FinnGen consortium ( = 218,792), and other consortia.

Association between homocysteine and nonalcoholic fatty liver disease: Mendelian randomisation study.

Background: Many observational studies explore the relationship between homocysteine (Hcy) and nonalcoholic fatty liver disease (NAFLD), whereas the causality of this association remains uncertain, especially in European populations. We performed a bidirectional Mendelian randomisation study to elucidate the causal association between Hcy and NAFLD. Furthermore, we explored the relationship of Hcy with liver enzymes, including alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Distinct causal effects of body fat distribution on cardiometabolic traits among children: Findings from the BCAMS study.

Background And Aims: Observational studies reveal that different body fat measures are associated with cardiometabolic disease with different effects. However, causality is not reflected by such observations. To explore and compare the causal relationships of general obesity (measured by body mass index (BMI)), adipose obesity (measured by fat mass percentage (FMP)) and central obesity (measured by waist-to-height ratio (WHtR)) with cardiometabolic traits among children.

A Novel Hierarchical Clustering Approach for Joint Analysis of Multiple Phenotypes Uncovers Obesity Variants Based on ARIC.

Genome-wide association studies (GWASs) have successfully discovered numerous variants underlying various diseases. Generally, one-phenotype one-variant association study in GWASs is not efficient in identifying variants with weak effects, indicating that more signals have not been identified yet. Nowadays, jointly analyzing multiple phenotypes has been recognized as an important approach to elevate the statistical power for identifying weak genetic variants on complex diseases, shedding new light on potential biological mechanisms.

Coding Variants are Relevant to the Expression of Obesity-Related Genes for Pediatric Adiposity.

Objective: Heredity has a remarkable effect on obesity in an obesogenic environment. Despite the numerous genetic variants that contribute to obesity-related traits, none has been identified in Chinese children. This study aimed to identify novel variants associated with childhood obesity in China.

A Novel Method for Mendelian Randomization Analyses With Pleiotropy and Linkage Disequilibrium in Genetic Variants From Individual Data.

Mendelian randomization makes use of genetic variants as instrumental variables to eliminate the influence induced by unknown confounders on causal estimation in epidemiology studies. However, with the soaring genetic variants identified in genome-wide association studies, the pleiotropy, and linkage disequilibrium in genetic variants are unavoidable and may produce severe bias in causal inference. In this study, by modeling the pleiotropic effect as a normally distributed random effect, we propose a novel mixed-effects regression model-based method PLDMR, pleiotropy and linkage disequilibrium adaptive Mendelian randomization, which takes linkage disequilibrium into account and also corrects for the pleiotropic effect in causal effect estimation and statistical inference.

A Novel Approach Integrating Hierarchical Clustering and Weighted Combination for Association Study of Multiple Phenotypes and a Genetic Variant.

As a pivotal research tool, genome-wide association study has successfully identified numerous genetic variants underlying distinct diseases. However, these identified genetic variants only explain a small proportion of the phenotypic variation for certain diseases, suggesting that there are still more genetic signals to be detected. One of the reasons may be that one-phenotype one-variant association study is not so efficient in detecting variants of weak effects.

A novel similarity score based on gene ranks to reveal genetic relationships among diseases.

Knowledge of similarities among diseases can contribute to uncovering common genetic mechanisms. Based on ranked gene lists, a couple of similarity measures were proposed in the literature. Notice that they may suffer from the determination of cutoff or heavy computational load, we propose a novel similarity score among diseases based on gene ranks.

Global synthesis of effects of plant species diversity on trophic groups and interactions.

Numerous studies have demonstrated that plant species diversity enhances ecosystem functioning in terrestrial ecosystems, including diversity effects on insects (herbivores, predators and parasitoids) and plants. However, the effects of increased plant diversity across trophic levels in different ecosystems and biomes have not yet been explored on a global scale. Through a global meta-analysis of 2,914 observations from 351 studies, we found that increased plant species richness reduced herbivore abundance and damage but increased predator and parasitoid abundance, predation, parasitism and overall plant performance.

Evidence on the causal link between homocysteine and hypertension from a meta-analysis of 40 173 individuals implementing Mendelian randomization.

Numerous researchers have investigated the associations among methylenetetrahydrofolate reductase gene (MTHFR) C677T polymorphism, homocysteine (Hcy) concentration, and hypertension. However, the results are controversial. Thus, a meta-analysis implementing Mendelian randomization approach was conducted to examine the hypothesis that elevated Hcy concentration plausibly contributes to increased risk of hypertension.

Plausible relationship between homocysteine and obesity risk via gene: a meta-analysis of 38,317 individuals implementing Mendelian randomization.

Objective: Numerous studies have explored the role of methylenetetrahydrofolate reductase gene () C677T polymorphism and homocysteine (Hcy) concentration in obesity, but the results are inconsistent. Hence, we performed a meta-analysis implementing Mendelian randomization approach to test the assumption that the increased Hcy concentration is plausibly related to the elevated risk of obesity.

Methods: Eligible studies were selected based on several inclusion and exclusion criteria.

Gene-gene interactions and associations of six hypertension related single nucleotide polymorphisms with obesity risk in a Chinese children population.

Obesity is a major risk for hypertension. However, the associations between hypertension susceptibility loci and the risk of obesity as well as the effects of gene-gene interactions are unclear, especially in the Chinese children population. Six single nucleotide polymorphisms (SNPs) (ATP2B1 rs17249754, CSK rs1378942, MTHFR rs1801133, CYP17A1 rs1004467, STK39 rs3754777, FGF5 rs16998073) were genotyped for 3503 Chinese children, aged 6-18 years.