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Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.

Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic

Genetic studies of body mass index yield new insights for obesity biology.

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genom…

Genome-wide profiling of salivary promoter-region DNA methylation in periodontitis: the Tromsø Study.

BACKGROUND: Methylation of DNA is an epigenetic reversible process that regulates gene expression. Aberrant promoter methylation is associated with chronic inflammation; however, the genome-wide DNA promoter methylation signature in periodontitis remains unexplored. METHODS: The present study is an epigenome-wide association study (EWAS) aimed at investigating salivary DNA methylation patterns within gene promoter regions in individuals with Stage III/IV periodontitis compared to healthy controls. Cases (all available individuals with Stage III/IV and probing pocket depths (PPD) > 5 mm, n = 50…

Analgesic drug usage is associated with differential methylation in lower back and neuropathic pain patients in the Quebec pain registry.

Analgesic drugs, which modulate nociception through various cellular pathways, are extensively used in pain treatment. However, their utility in blocking pain signaling is offset by side effects and potential for misuse. The long-term effects of exposure to these drugs remain poorly understood and may involve epigenetic alterations to gene expression patterns, including differential methylation of gene regulatory regions. We hypothesized that individuals with pain conditions, enrolled in a longitudinal pain registry and exposed to different analgesic drugs, would later exhibit significant diff

Cross-ancestry polygenic risk scores enhance Alzheimer's disease risk prediction in multiethnic cohorts.

INTRODUCTION: Genome-wide association studies (GWAS) have identified 80+ genetic loci associated with Alzheimer's disease (AD), enabling the development of polygenic risk scores (PRS). However, the predictive accuracy of PRS in diverse populations remains low. Here, we evaluated the predictive accuracy of single-, multi-, and cross-ancestry AD-PRS models across multi-ancestral populations. METHODS: We used AD GWAS summary statistics from European, African, Admixed American, and East Asian populations to construct AD-PRS for each target population. Model performance was assessed by estimating

Мультиэнштейная геномная ассоциация и мультиомикальный анализ позволяют выявить специфичные особенности многоклерозной генетики.

Множественный склероз (MS) — хроническое воспалительное заболевание центральной нервной системы, характеризующееся обезвоживанием, распространяющимся в пространстве и во времени. Здесь мы провели исследование ассоциации генома (GWAS) с использованием 688 Количество дел, связанных с НР и 205,199 :: контроль со стороны японского населения и выявление важных связей в основном сложном регионе, связанном с гистокомпьютерностью, и в 11q24 году вариант риска, учитывающий специфику населения. С помощью межнаселенных метаанализов GWAS с использованием всего 29,374 случаи и случаи 1,843,563 контроля с 4

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination disseminated in space and time. Here we performed a genome-wide association study (GWAS) using 688 MS cases and 205,199 controls from the Japanese population and identified significant associations in the major histocompatibility complex reg…

A pleiotropy scan to discover new susceptibility loci for pancreatic ductal adenocarcinoma.

Pleiotropic variants (i.e. genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleio … ability of association with other traits, 61 052 variants reported to be associated by at least one genome-wide association study with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16 055 pancreatic ductal adenocarcinoma (PDAC) cases and 212 149 controls. The meta-analysis of the two phases …

DNA methylation signatures of Life's Essential 8 and their implications for dementia.

BACKGROUND: As dementia cases continue to rise, effective prevention strategies are urgently needed. However, objective biomarkers that directly reflect lifestyle factors remain limited. Life's Essential 8 (LE8) is a composite of modifiable cardiovascular health metrics, and lower LE8 has been consistently associated with increased risk of dementia. In this study, we aimed to identify DNA methylation biomarkers associated with LE8 scores and investigate their relevance for dementia risk. METHODS: We performed an epigenome-wide association study of 273 stroke-free, self-identified Hispanic adu…

Exploring the Impact of 731 Immunophenotypes on Alopecia Areata Risk: A Mendelian Randomization Analysis With Plasma Metabolites as Mediators.

OBJECTIVE: This study aimed to delineate the causal relationship between immunophenotypes and alopecia areata (AA) and to assess the intermediary role of plasma metabolites. METHODS: The authors utilized bidirectional Mendelian randomization (MR) to parse the causal associations between 731 immunophenotypes and AA using genome-wide association study (GWAS) summary statistics from 767 cases and 394,105 controls. A 2-step MR strategy was adopted to quantify the influence of 1400 plasma metabolites on AA through their impacts on immunophenotypes. RESULTS: The MR findings indicated that an eleva…

Causality between coffee intake and bone health: A Mendelian randomization study.

Observational studies have reported associations between coffee intake and osteoarthritis (OA), rheumatoid arthritis (RA), and osteoporosis (OP). However, it remains unknown whether these relationships are causal. In this study, we applied a 2-sample bidirectional Mendelian randomization (MR) analysis to comprehensively evaluate the causal association between coffee intake and OA, RA, and OP. Genetic data for OA (40,425 controls and 10,083 cases), RA (22,350 controls and 74,823 cases), OP (476,847 controls and 7751 cases), and coffee intake (263,464 Europeans) were obtained from the UK Biobank

Assessing the relationship between wrist synovitis and anxiety: a study using clinical statistics and Mendelian randomization analysis.

BACKGROUND: Wrist synovitis often leads to persistent pain, swelling, and limited mobility, causing significant functional impairment and psychological distress, including anxiety. Although arthroscopic synovectomy can alleviate physical symptoms, whether it also improves anxiety and the causal relationship between synovitis and anxiety remains unclear. METHODS: A prospective study was conducted on 44 patients diagnosed with wrist synovitis who underwent arthroscopic synovectomy. Patients were assessed preoperatively and at 2 and 4 weeks postoperatively using the Visual Analog Scale (VAS), Ma

Identification of genetically-supported new drug targets for osteomyelitis based on druggable genomes.

BACKGROUND: Limited drug treatment data are available for osteomyelitis (OM), an inflammatory bone condition secondary to infection. Given i … lected as instrumental variables for MR analysis using blood QTL data and independent osteomyelitis genome-wide association study datasets from UK Biobank and FinnGen R10. A random-effects model meta-analysis combining the results from two datasets was performed. Bayesian co-localization analysis was conducted to validate the targets. Sensitivity analyses were performed using …

Multiancestry Transcriptome-Wide Association Study Identifies Candidate Genes Associated with Hepatoblastoma.

BACKGROUND: Hepatoblastoma (HB) is a rare embryonal liver tumor, with an increasing global incidence that underscores the need to understand … NS: We pinpointed eight potential genes associated with HB using data from an ongoing multiancestry genome-wide association study. IMPACT: We conducted the largest HB TWAS to date, prompting further exploration of genes.

SCN1A pathogenic variants do not have a distinctive blood-derived DNA methylation signature.

DNA methylation signatures ("episignatures") can be used as biomarkers of genetic aberrations, clinical phenotypes, and environmental exposures in rare diseases. Episignatures are utilized in molecular diagnostics and can clarify variants of uncertain significance. A growing number of disease genes, including epilepsy genes, exhibit robust and reproducible episignatures. However, whether SCN1A, the most prominent epilepsy gene, has one or more episignatures has not yet been determined. We generated genome-wide DNA methylation data and performed episignature analysis on 64 individuals with Drav

Nasopharyngeal Microbiome-Epigenome-Wide Association Analysis in Infants With Severe Bronchiolitis.

BACKGROUND: Bronchiolitis exposes infants to both acute burdens (e.g., hospitalization in cases of severe bronchiolitis) and increased risks for chronic respiratory sequelae (e.g., asthma). In severe bronchiolitis, recent evidence suggests distinct pathobiological roles of microbiota (e.g., viruses, bacteria) and host responses influenced by genetic and epigenetic factors. However, the relationship of airway microbiota with host DNA methylation (DNAm) in infants with severe bronchiolitis remains unknown. METHODS: In a multi-center prospective cohort of 504 multi-ethnic infants with severe bro

Does Gastroesophageal Reflux Disease Increase the Risk of Sepsis and Its 28-day Mortality? A Causal Study Using a Mendelian Randomization Approach.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder. Recent studies indicate that GERD may exert systemic effects, potentially elevating the risk of severe infections, including sepsis. Nevertheless, the causal relationship between GERD and sepsis, as well as sepsis-related 28-day mortality, remains uncertain. AIM: The aim of this study is to investigate the causal relationship between GERD and the risk of sepsis, including 28-day mortality of sepsis. METHODS: This study utilized a two-sample Mendelian Randomization (MR) approach to analyze data from p

L-shaped association of triglyceride glucose index and sensorineural hearing loss: results from a cross-sectional study and Mendelian randomization analysis.

BACKGROUND: The association between the sensorineural hearing loss (SNHL) and triglyceride-glucose (TyG) index remains inadequately understood. This investigation seeks to elucidate the connection between the TyG index and SNHL. METHODS: In this cross-sectional study, we utilized datasets sourced from the National Health and Nutrition Examination Survey (NHANES). A comprehensive analysis was conducted on 1,851 participants aged 20 to 69, utilizing complete audiometry data from the NHANES database spanning from 2007 to 2018. All enrolled participants had accessible hearing data, and the averag

Association of asthma and bronchiectasis: Mendelian randomization analyses and observational study.

BACKGROUND: Previous studies have demonstrated that asthma is closely associated with bronchiectasis, however, the causal relationship between asthma and bronchiectasis has not been investigated in depth. Therefore, this study aims to explore the causal relationship and to identify potential factors that mediate between these two diseases. METHOD: All the necessary summarized information were obtained from publicly available genome-wide association study (GWAS). Two-sample Mendelian randomization (two-sample MR) was employed to explore the causal relationship between asthma and bronchiectasis…

The adverse effect of mood swings on the risk of cardiovascular diseases: Evidence from Mendelian randomization analysis.

Recent studies have explored the impact of personality traits, including mood swings, on physical health. However, it remains unclear whether there is a direct cause-and-effect link between mood swings and cardiovascular diseases (CVDs). A STROBE-compliant cross-sectional observational study was conducted and analyzed using a two-sample Mendelian randomization (MR) approach to examine the potential causal relationship between mood swings and a range of CVDs, such as arrhythmia, artery aneurysm, coronary heart disease (CHD), heart failure, hypertension, stroke, ischemic stroke, and peripheral a

Association of educational attainment with esophageal cancer, Barrett's esophagus, and gastroesophageal reflux disease, and the mediating role of modifiable risk factors: A Mendelian randomization study.

BACKGROUND: Observational studies have reported that educational attainment has been related to the risk of esophageal cancer (EC) and its precancerous lesions. However, the causal relationship remains controversial. We aimed to apply the Mendelian randomization (MR) design to determine the causal associations between genetically predicted educational attainment and EC, Barrett's esophagus (BE), and gastroesophageal reflux disease (GERD), and to explore whether modifiable risk factors play a mediating role. METHODS: Using summary statistics from genome-wide association studies (GWASs) based o