Causal Relationships between Iron Status and Nonalcoholic Fatty Liver Disease: Two-Sample, Multivariable, and Two-Step Mendelian Randomization.

Background: Nonalcoholic fatty liver disease (NAFLD) was clinically documented to be accompanied by iron homeostasis imbalances, however, the causal relationship between them remains unclear. Therefore, this study aimed to examine the relationship between iron homeostasis indicators (serum iron, ferritin, transferrin, total iron binding capacity (TIBC), and transferrin saturation (TSAT)) and NAFLD risk.

Methods: We applied two-sample Mendelian randomization (MR) to assess the effects of genetic liability to iron homeostasis indicators (N = 43,220-246,139) on NAFLD risk (N = 377,988) in individuals of European ancestry.

Association between frailty and the progression trajectories of stroke and dementia comorbidity: insights from observational and genetic analyses.

Background: The relationship between frailty and the progression trajectories of stroke-dementia comorbidity remains inconclusive. This study aimed to determine whether there are associations between frailty and the progression trajectories of stroke-dementia comorbidity, including the transitions from enrollment to incident stroke/dementia, progression to stroke-dementia comorbidity, and ultimately to mortality.

Methods: This prospective study was conducted based on the UK Biobank cohort.

An integrated prognosis prediction model based on real-word clinical characteristics for immunotherapy in advanced esophageal squamous cell carcinoma.

Introduction: Immune checkpoint inhibitors (ICIs) benefit only a subset of patients in advanced esophageal squamous cell carcinoma (ESCC). Our study aims to develop and validate a clinically accessible model to better identify those who may respond to ICIs.

Methods: This study enrolled advanced ESCC patients treated with ICIs at Peking University Cancer Hospital from January 14, 2016, to January 26, 2024 for the training cohort and at Harbin Medical University Cancer Hospital between January 10, 2019, and July 6, 2022 for the validation cohort.

Accelerated biological age mediates the associations between sleep patterns and chronic respiratory diseases: Findings from the UK Biobank Cohort.

Background: Unhealthy sleep patterns and accelerated biological age are frequently associated with multiple chronic respiratory diseases (CRDs), including COPD, asthma, and interstitial lung disease (ILD). However, few studies have explored the role of biological age in the relationship between sleep patterns and CRDs.

Objectives: To explore the association between sleep patterns and CRD, and the extent to which biological age mediates the relationship between sleep patterns and CRD.

Unraveling shared susceptibility loci and Mendelian genetic associations linking educational attainment with multiple neuropsychiatric disorders.

Background: Empirical studies have demonstrated that educational attainment (EA) is associated with neuropsychiatric disorders (NPDs), suggesting a shared etiological basis between them. However, little is known about the shared genetic mechanisms and causality behind such associations.

Methods: This study explored the shared genetic basis and causal relationships between EA and NPDs using the high-definition likelihood (HDL) method, cross phenotype association study (CPASSOC), transcriptome-wide association study (TWAS), and bidirectional Mendelian randomization (MR) with summary-level data for EA ( = 293,723) and NPDs ( range = 9,725 to 455,258).

Association between circulating biomarkers and non-alcoholic fatty liver disease: An integrative Mendelian randomization study of European ancestry.

Background And Aim: Circulating biomarkers provide potential diagnostic or prognostic information on disease presentation, progression or both. Early detection of circulating risk biomarkers is critical for non-alcoholic fatty liver disease (NAFLD) prevention. We aimed to systematically assess the potential causal relationship of genetically predicted 60 circulatory biomarkers with NAFLD using a two-sample Mendelian randomization (MR) design.

Depression and risk of gastrointestinal disorders: a comprehensive two-sample Mendelian randomization study of European ancestry.

Background: Major depressive disorder (MDD) is clinically documented to co-occur with multiple gastrointestinal disorders (GID), but the potential causal relationship between them remains unclear. We aimed to evaluate the potential causal relationship of MDD with 4 GID [gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), peptic ulcer disease (PUD), and non-alcoholic fatty liver disease (NAFLD)] using a two-sample Mendelian randomization (MR) design.

Methods: We obtained genome-wide association data for MDD from a meta-analysis ( = 480 359), and for GID from the UK Biobank ( ranges: 332 601-486 601) and FinnGen ( ranges: 187 028-218 792) among individuals of European ancestry.

Genetic support of a causal relationship between cannabis use and educational attainment: a two-sample Mendelian randomization study of European ancestry.

Background And Aims: Excessive cannabis use may lead to lower educational attainment. However, this association may be due to confounders and reverse causality. We tested the potential causal relationship between cannabis use disorder (CUD) or life-time cannabis use (LCU) and educational attainment.

Sleep and Late-Onset Alzheimer's Disease: Shared Genetic Risk Factors, Drug Targets, Molecular Mechanisms, and Causal Effects.

Late-onset Alzheimer's disease (AD) is associated with sleep-related phenotypes (SRPs). The fact that whether they share a common genetic etiology remains largely unknown. We explored the shared genetics and causality between AD and SRPs by using high-definition likelihood (HDL), cross-phenotype association study (CPASSOC), transcriptome-wide association study (TWAS), and bidirectional Mendelian randomization (MR) in summary-level data for AD ( = 455,258) and summary-level data for seven SRPs (sample size ranges from 359,916 to 1,331,010).

Shared Genetic Basis and Causal Relationship Between Television Watching, Breakfast Skipping and Type 2 Diabetes: Evidence From a Comprehensive Genetic Analysis.

Background: Epidemiological investigations have established unhealthy lifestyles, such as excessive leisurely sedentary behavior (especially TV/television watching) and breakfast skipping, increase the risk of type 2 diabetes (T2D), but the causal relationship is unclear. We aimed to understand how single nucleotide variants contribute to the co-occurrence of unhealthy lifestyles and T2D, thereby providing meaningful insights into disease mechanisms.

Methods: Combining summary statistics from genome-wide association studies (GWAS) on TV watching ( = 422218), breakfast skipping ( = 193860) and T2D ( = 159208) in European pedigrees, we conducted comprehensive pairwise genetic analysis, including high-definition likelihood (HDL-method), cross-phenotype association studies (CPASSOC), GWAS-eQTL colocalization analysis and transcriptome-wide association studies (TWAS), to understand the genetic overlap between them.