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Reactive astrocyte-related pathogenic genes in Parkinson's disease: A multi-omics Mendelian randomization study.

BackgroundReactive astrocytes are one of the pathological features of Parkinson's disease (PD) and are associated with neuroinflammation and neuronal damage.ObjectiveTo explore the causal relationship between reactive astrocyte-related genes and PD through the summary data-based Mendelian randomization (SMR).MethodsWe combined these reactive astrocyte-related Quantitative Trait Loci (QTLs) data with PD genome-wide association study (GWAS) statistics. Using SMR, we explored causal links between gene expression, methylation and protein levels (pQTL) with PD, which were validated through colocali…

Differentially expressed genes and therapeutic targets for nonalcoholic fatty liver disease from transcriptomic techniques.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver conditions globally. Lifestyle interventions are currently … dentify gene expression changes in NAFLD samples relative to healthy ones. Subsequently, expression-quantitative trait loci (eQTL) and Mendelian randomization (MR) analyses were applied to evaluate the relationship between these genes and NAFLD. Additionally, the potential functional pathways of differentially expressed genes were explored using enrichment analyses. A va …

Uncovering potential therapeutic targets for autoimmune hepatitis using proteome-wide Mendelian randomization.

Autoimmune hepatitis (AIH) is a chronic inflammatory disorder caused by an aberrant immune response directed against liver tissues. However, current treatments for AIH are insufficient in preventing disease progression, managing relapses, and minimizing adverse effects. Therefore, new treatments are urgently needed to improve the management of AIH. Protein quantitative trait loci data for 2940 plasma proteins were obtained from the UK Biobank Pharma Proteomics Project. Genetic association data for AIH were obtained from the FinnGen Consortium (including 264 AIH patients and 3,72,273 healthy co…

DNA methylation and bronchiectasis: a Mendelian randomization analysis to investigate causal link and therapeutic target.

This study aims to discover drug targeted genes and explore the potential epigenetics mechanisms in bronchiectasis. Cis-expression quantitative trait locus (eQTL) was obtained as exposure, and bronchiectasis from the FinnGen cohort was used as outcome. Mendelian Randomization (MR) was performed to identify therapeutic targets associated with bronchiectasis. Colocalization and summary-data-based MR (SMR) analyses were carried out to further confirm the causal roles of candidate genes in bronchiectasis. The value of these drug targets was validated via drug prediction and molecular docking. Fina

Novel drug targets for delirium based on genetic causality.

BACKGROUND: Effective treatment and prevention of delirium remain challenging, largely due to the limited efficiency in identifying and validating drug targets. To address this gap, we performed a systematic Mendelian Randomization (MR) study of the druggable genome to identify potential therapeutic targets for delirium. METHODS: To identify therapeutic targets for delirium, we conducted MR and colocalization analyses using cis-eQTL data (31,684 blood samples and 1387 brain samples) and genome-wide association study (GWAS) data for delirium (discovery cohort N = 431,880; validation cohort N =

Systematic Mendelian randomization of the human plasma proteome to identify therapeutic targets linking aging and frailty to perioperative delirium.

BACKGROUND: Perioperative delirium is a growing concern in the aging population, posing significant risks to frail elderly patients. While frailty is associated with delirium, the underlying mechanisms remain unclear. METHODS: We conducted an analysis of data derived from 3788 plasma proteins in a protein quantitative trait locus (pQTL) study encompassing 4709 participants. Utilizing Mendelian randomization (MR) in conjunction with genome-wide association study (GWAS) data, we identified proteins that exhibit significant associations with delirium. Additionally, we investigated the bidirectio

Genetic correlation analysis between sepsis and hematological traits: Identifying shared genomic regions.

BACKGROUND: Sepsis, dysregulated cascades of inflammatory response to infection, remains a critical clinical condition, leading to morbidity and mortality. Better understanding of the genetic basis underlying sepsis has the potential to better prevent and treat this potentially life-threatening condition. Recent studies have identified genetic variants for sepsis and accumulated evidence for the relevance of hematological traits. However, genetic correlation analysis, testing the hypothesis of shared genetic underpinning of sepsis and hematological traits, as well as identifying shared specifi

Genetic Loci Influencing Cue-Reactivity in Heterogeneous Stock Rats.

Addiction vulnerability is associated with the tendency to attribute incentive salience to reward predictive cues. Both addiction and the at … rewarded presentations of the cue using the conditioned reinforcement procedure. GWAS identified 14 quantitative trait loci (QTLs) for 11 of the 12 traits across both tasks. Interval sizes of these QTLs varied widely. Seven traits shared a QTL on chromosome 1 that contained a few genes (e.g., Tenm4, Mir708) that have been associated with substance use disorders and other …

Fine-mapping genomic loci refines bipolar disorder risk genes.

Bipolar disorder is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 bipolar disorder risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci and prioritized 17 likely causal SNPs for bipolar disorder. We mapped these SNPs to genes and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci and results from rare variant exome …

Uncovering therapeutic targets for Pre-eclampsia and pregnancy hypertension via multi-tissue data integration.

BACKGROUND: Pre-eclampsia (PE) and pregnancy hypertension (PH) are common and serious complications during pregnancy, which can lead to maternal and fetal death in severe cases. Therefore, further research on the potential therapeutic targets of PE and PH is of great significance for developing new treatment strategies. METHODS: This study used the summary data-based Mendelian randomization (SMR) method to analyze expression quantitative trait loci (eQTL) data from blood, aorta, and uterus with Genome-wide association studies (GWAS) data on PE and PH, exploring potential genetic loci involved…

Atad1 Is a Potential Candidate Gene for Prepulse Inhibition.

Background/Objectives: Prepulse inhibition (PPI) is a robust, reproducible phenotype associated with schizophrenia and other psychiatric disorders. This study was carried out to identify gene(s) influencing PPI. Methods: We performed Quantitative Trait Locus (QTL) analysis of PPI in 59 strains from the BXD recombinant inbred (BXD RI) mouse family and used a 2-LOD region for candidate gene identification. Genes significantly correlated with the candidate gene were identified based on genetic, partial, and literature correlation, and were further studied through gene enrichment and protein-prote

Multi-omics tests identify novel shared genetic mechanisms of primary biliary cholestasis and sarcopenia.

Primary biliary cholangitis (PBC) may affect skeletal muscles through the muscle-liver axis, subsequently leading to sarcopenia. Our study aims to explore the unclear genetic relationships between PBC and sarcopenia. We investigated the shared genetic architecture of PBC and sarcopenia using advanced statistical genetics methods and genome-wide association summary data. We employed global and local genetic correlation to gain potential shared biological mechanisms. We identified risk single nucleotide polymorphisms (SNPs) and functionally annotated genomic multi-markers by conducting the unifi

Comprehensive mendelian randomization analysis of human plasma proteome to identify potential drug targets for essential tremor.

We performed a systematic causal analysis of the plasma proteome, to discover potential protein markers and therapeutic targets for essential tremor (ET). Protein quantitative trait loci (pQTLs) of 4853 plasma proteins were derived from 7 published genome-wide association studies of the plasma proteome. A 2-sample Mendelian randomization (MR) study was conducted to assess the potential causal relationships between 4853 plasma proteins and ET. Summary-data-based MR and Bayesian colocalization analyses were performed to confirm the causal roles of the candidate proteins. Phenome-wide-MR (Phe-MR)…

Comprehensive genetic analysis based on multi - omics reveals novel therapeutic targets for mitral valve prolapse and drug molecular dynamics simulation.

OBJECTIVE: Mitral valve prolapse (MVP), the most prevalent primary valvular disease, serves as a direct risk factor for multiple cardiovascular disorders and exhibits a high prevalence in the general population. As no specific pharmacological therapies currently exist for MVP, the identification of precise therapeutic targets is imperative. METHOD: We conducted comprehensive causal genetic inference by integrating genetic data from expression quantitative trait loci (eQTL) and genome-wide association studies (GWAS). Analytical approaches included Mendelian Randomization (MR), colocalization a…

Является ли DEXI множественным склерозом удобочитаемым геном?

Генетический ландшафт множественного склероза (MS) был тщательно просчитан, что позволило глубже понять молекулярные механизмы расстройства. В ходе первых исследований были выявлены ключевые гены, связанные с иммунной системой, в частности с Т клетками, которые имеют решающее значение для MS-чувствительности. В ходе последующих широкомасштабных исследований, проведенных в рамках всей ассоциации генома (GWAS), было выявлено более 200 генетических вариантов, связанных с MS, что выявило сложную взаимосвязь между риском, связанным с MS, и генами, вовлеченными в различные процессы в рамках адаптивн

Совпадение в аннотации оригинала
The genetic landscape of multiple sclerosis (MS) has been extensively mapped, yielding significant insights into the molecular mechanisms of … rders. Notably, several autoimmune-associated genetic variants in CLEC16A introns act as expression quantitative trait loci for the dexamethasone-induced protein (DEXI gene, adding DEXI to the growing list of MS susceptibility genes. This review explores the molecular and functional characterization of DEXI with a particular focus on recent advances in understanding its …

Сексуальные патогенные гены, связанные с Хормоном, в многоразовом склерозе: многоомикальное исследование менделии.

Множественный склероз (MS) — хроническое аутоиммунное заболевание со сложными этиологиями, включая генетические факторы. Сексуальные гормоны были замешаны в патогенезе MS, однако основные генетические механизмы остаются неясными. В этом исследовании использовался многомерный подход к произвольной менделизации (MR) для оценки причинно-следственных связей между генами, связанными с сексуальными гормонами, и MS. Мы использовали сводные данные, полученные в ходе исследований по общегеномной ассоциации (GWAS) и основанных на крови количественных loci (mQTLs), выражение QTL (eQTLs) и протеомический

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic autoimmune disease with complex etiologies, including genetic factors. Sex hormones have been implicate … S. We utilized summary data from genome-wide association studies (GWAS) and blood-based methylation quantitative trait loci (mQTLs), expression QTL (eQTLs), and proteomic QTL (pQTLs). The analysis employed the summary data-based MR (SMR) method and the HEIDI test for pleiotropy. Colocalization analysis identified shared genetic determinants, validated in UK Biobank and F …

From proteome to pathogenesis: investigating polycystic ovary syndrome with Mendelian randomization analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is defined by oligo/anovulation, hyperandrogenism, and polycystic ovaries with uncertain pathogenesis. The proteome represents a substantial source of therapeutic targets, and their coding genes may elucidate the mechanisms underlying PCOS. However, reports on the profiles of the human plasma protein-coding genes and PCOS are limited. Here, we aimed to investigate novel biomarkers or drug targets for PCOS by integrating genetics and the human plasma proteome. METHODS: Our study acquired the protein quantitative trait loci from DECODE Genetics, offe…

A multi-ancestry genome-wide association study identifies novel candidate loci in the RARB gene associated with hypertensive disorders of pregnancy.

Genetic factors related to pregnancy-related traits are understudied, especially in ancestrally diverse cohorts. To assess maternal contribu … associations near RARB with a meta-analysis of PEGS and the UKBB. We also identified cis-expression quantitative trait loci in the candidate region associated with decreased RARB expression in macrophage cells exposed to Salmonella. Chromatin mapping in FUMA identified a significant interaction within chromosome 3's enhancer and open chromatin regions, with strong effect …

Genetic insights into drug targets for sporadic Creutzfeldt-Jakob disease: Integrative multi-omics analysis.

OBJECTIVE: Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal rapidly progressive neurodegenerative disorder with no effective therapeutic interventions. We aimed to identify potential genetically-supported drug targets for sCJD by integrating multi-omics data. METHODS: Multi-omics-wide association studies, Mendelian randomization, and colocalization analyses were employed to explore potential therapeutic targets using expression, single-cell expression, DNA methylation, and protein quantitative trait locus data from blood and brain tissues. Outcome data was from a case-control genome-wide

Expression quantitative trait methylation analysis elucidates gene regulatory effects of DNA methylation: the Framingham Heart Study.

Expression quantitative trait methylation (eQTM) analysis identifies DNA CpG sites at which methylation is associated with gene expression. The present study describes an eQTM resource of CpG-transcript pairs derived from whole blood DNA methylation and RNA sequencing gene expression data in 2115 Framingham Heart Study participants. We identified 70,047 significant cis CpG-transcript pairs at p < 1E-7 where the top most significant eGenes (i.e., gene transcripts associated with a CpG) were enriched in biological pathways related to cell signaling, and for 1208 clinical traits (enrichment false