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Beyond black and white: dissecting the genetic basis of skin depigmentation in Nellore cattle.

Depigmentation defects in cattle are characterized by the absence of pigment in specific skin regions, increasing susceptibility to health issues and often leading to early culling. In Nellore cattle, depigmentation is primarily observed at the tail tip, mucous membranes, and as small patches across the body. This study aimed to estimate genetic parameters and perform a genome-wide association study (GWAS) for depigmentation in Nellore cattle. Data were sourced from the DeltaGen® breeding program, provided by Gensys®. Phenotypic records included 182,964 Nellore cattle, with a 6.8% incidence of

Методы машинного обучения для классификации множественного склероза и болезни Альцгеймера с использованием геномных данных.

Сложные заболевания создают трудности в прогнозировании из-за их многофакторного и полигенного характера. В этом исследовании используется машинное обучение (ML) для анализа геномных данных из британского биобанка с целью прогнозирования геномной предрасположенности к таким сложным болезням, как множественный склероз (MS) и болезнь Альцгеймера (AD). Мы проверили логистическую регрессию (LR), методы ансамбля деревьев и модели глубокого обучения с этой целью. LR продемонстрировал замечательную стабильность в различных поднаборах данных, превосходя глубинные подходы к обучению, которые продемонст

Совпадение в аннотации оригинала
Complex diseases pose challenges in prediction due to their multifactorial and polygenic nature. This study employed machine learning (ML) t … s disease. The highest-prioritized genomic variants in MS were identified as expression or splicing quantitative trait loci located in non-coding regions within or near genes associated with the immune response, with a prevalence of human leukocyte antigen (HLA) gene annotations. Our findings shed light on both the potential and the challenges of employing ML to capture …

Identification of Potential Causal Genes for Neurodegenerative Diseases by Mitochondria-Related Genome-Wide Mendelian Randomization.

Current research lacks comprehensive investigations into the potential causal link between mitochondrial-related genes and the risk of neurodegenerative diseases (NDDs). We aimed to identify potential causative genes for five NDDs through an examination of mitochondrial-related gene expression levels. Through the integration of summary statistics from expression quantitative trait loci (eQTL) datasets (human blood and brain tissue), mitochondrial DNA copy number (mtDNA-CN), and genome-wide association studies (GWAS) datasets of five NDDs from European ancestry, we conducted a Mendelian randomi…

Inflammatory proteins and hidradenitis suppurativa: Insights from genetic correlation and Mendelian randomization.

Previous research has highlighted a significant association between inflammatory proteins and the development and progression of hidradeniti … d out to explore reverse causality. The data set for 91 CIPs was derived from a genome-wide protein quantitative trait loci study, while HS-related data were acquired from the FinnGen study. Moreover, the stability of the causal relationships was assessed via sensitivity analyses, encompassing tests for pleiotropy, heterogeneity, and leave-one-out analysis. The LDSC anal …

[Identification of prognostic genes in prostate cancer by single-cell sequencing combined with Mendelian randomization].

OBJECTIVE: To identify the key genes involved in the development and progression of prostate cancer (PCa) and those associated with the prog … e. Then we downloaded the single nucleotide polymorphism (SNP) loci corresponding to the expression quantitative trait loci (eQTL) of these genes from the UK Biobank (UKB) database, and the clinical data and corresponding gene expression data on PCa patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), followed by univariate COX regression analy …

Plasma proteins and inflammatory dermatoses: proteome-wide Mendelian randomization and colocalization analyses.

Current genome-wide association studies (GWAS) of plasma proteomes provide additional possibilities for finding new drug targets for inflammatory dermatoses. We performed proteome-wide Mendelian randomization (MR) and colocalization analyses to identify novel potential drug targets for inflammatory dermatoses. We performed MR and colocalization analysis using genetic variation as instrumental variables to determine the causal relationship between circulating plasma proteins and inflammatory dermatoses. 5 plasma proteins were found to be causally associated with dermatitis eczematosa, SLE, urti

Sarcopenia and immune-mediated inflammatory diseases: Evaluating causality and exploring therapeutic targets for sarcopenia through Mendelian randomization.

BACKGROUND: An increasing body of evidence has revealed the association between immune-mediated inflammatory diseases (IMIDs) and sarcopenia … xposure of druggable genes, including genetic variants within or nearby drug targets and expression quantitative trait loci (eQTLs) of drug targets. Two-sample MR and summary-data-based MR (SMR) were used to calculate effect estimates, and sensitivity analyses were implemented for robustness. Drug tractability, gene enrichment analysis, and protein-protein interaction (P …

Functional genomics implicates natural killer cells in the pathogenesis of ankylosing spondylitis.

Multiple lines of evidence indicate that ankylosing spondylitis (AS) is a lymphocyte-driven disease. However, which lymphocyte populations are critical in AS pathogenesis is not known. In this study, we aimed to identify the key cell types mediating the genetic risk in AS using an unbiased functional genomics approach. We integrated genome-wide association study (GWAS) data with epigenomic and transcriptomic datasets of human immune cells. To quantify enrichment of cell type-specific open chromatin or gene expression in AS risk loci, we used three published methods-LDSC-SEG, SNPsea, and scDRS-

Druggable genome-wide Mendelian randomization for identifying the role of integrated stress response in therapeutic targets of bipolar disorder.

For bipolar disorder (BD), the inconsistency of treatment guidelines and the long phases of pharmacological adjustment remain major challenges. BD is known to be comorbid with many medical and psychiatric conditions and they may share inflammatory and stress-related aetiologies, which could give rise to this association. The integrated stress response (ISR) responds to various stress conditions that lead to alterations in cellular homeostasis. However, as a causative mechanism underlying cognitive deficits and neurodegeneration in a broad range of brain disorders, the impact of ISR on BD is un

Genome-wide detection of changes in allelic frequency in Landrace pigs selected for resistance to mycoplasma pneumonia of swine.

Closed-pig line breeding could change the genetic structure at a genome-wide scale because of the selection in a pig breeding population. We … y spread across the genome, and a few of these selected regions overlapped with previously detected quantitative trait loci for MPS and immune-related traits. Our results indicated that the considerable changes in allele frequency were identified in many regions across the genome by closed-pig line breeding based on estimated breeding value.

Integrative Functional Genomics Identifies Systemic Lupus Erythematosus Causal Genetic Variant in the IRF5 Risk Locus.

OBJECTIVE: IRF5 plays a crucial role in the development of lupus. Genome-wide association studies have identified several systemic lupus erythematosus (SLE) risk single-nucleotide polymorphisms (SNPs) enriched in the IRF5 locus. However, no comprehensive genome editing-based functional analysis exists to establish a direct link between these variants and altered IRF5 expression, particularly for enhancer variants. This study was undertaken to dissect the regulatory function and mechanisms of SLE IRF5 enhancer risk variants and to explore the utilization of clustered regularly interspaced short

Characterizing the genetic basis of copper toxicity in Drosophila reveals a complex pattern of allelic, regulatory, and behavioral variation.

A range of heavy metals are required for normal cell function and homeostasis. However, the anthropogenic release of metal compounds into soil and water sources presents a pervasive health threat. Copper is one of many heavy metals that negatively impacts diverse organisms at a global scale. Using a combination of quantitative trait locus (QTL) mapping and RNA sequencing in the Drosophila Synthetic Population Resource, we demonstrate that resistance to the toxic effects of ingested copper in D. melanogaster is genetically complex and influenced by allelic and expression variation at multiple l

Genetic correlations between traits associated with hyperuricemia, gout, and comorbidities.

Hypertension, obesity, chronic kidney disease and type 2 diabetes are comorbidities that have very high prevalence among persons with hyperuricemia (serum urate > 6.8 mg/dL) and gout. Here we use multivariate genetic models to test the hypothesis that the co-association of traits representing hyperuricemia and its comorbidities is genetically based. Using Bayesian whole-genome regression models, we estimated the genetic marker-based variance and the covariance between serum urate, serum creatinine, systolic blood pressure (SBP), blood glucose and body mass index (BMI) from two independent fami

QTL Mapping of Intestinal Neutrophil Variation in Threespine Stickleback Reveals Possible Gene Targets Connecting Intestinal Inflammation and Systemic Health.

Selection, via host immunity, is often required to foster beneficial microbial symbionts and suppress deleterious pathogens. In animals, the host immune system is at the center of this relationship. Failed host immune system-microbial interactions can result in a persistent inflammatory response in which the immune system indiscriminately attacks resident microbes, and at times the host cells themselves, leading to diseases such as Ulcerative Colitis, Crohn's Disease, and Psoriasis. Host genetic variation has been linked to both microbiome diversity and to severity of such inflammatory disease

Assessment of the expression pattern of mTOR-associated lncRNAs and their genomic variants in the patients with breast cancer.

The mechanistic target of rapamycin (mTOR) is a fundamental component of a signaling pathway that is involved in the pathogenesis of breast cancer via different mechanisms. This pathway is functionally linked with a number of small nucleolar RNA host genes (SNHGs). In the present project, we have searched for the expression quantitative trait loci (eQTLs) within SNHGs that are possibly involved in the pathogenesis of breast cancer. Following this in silico step, we have assessed expression levels of mTOR and four SNHGs in malignant and nonmalignant samples obtained from 80 patients with breast…

pSBVB: A Versatile Simulation Tool To Evaluate Genomic Selection in Polyploid Species.

Genomic Selection (GS) is the procedure whereby molecular information is used to predict complex phenotypes and it is standard in many animal and plant breeding schemes. However, only a small number of studies have been reported in horticultural crops, and in polyploid species in particular. In this paper, we have developed a versatile forward simulation tool, called polyploid Sequence Based Virtual Breeding (pSBVB), to evaluate GS strategies in polyploids; pSBVB is an efficient gene dropping software that can simulate any number of complex phenotypes, allowing a very flexible modeling of phen

Determining the genetic basis of anthracycline-cardiotoxicity by molecular response QTL mapping in induced cardiomyocytes.

Anthracycline-induced cardiotoxicity (ACT) is a key limiting factor in setting optimal chemotherapy regimes, with almost half of patients ex … o cell damage, which in turn is associated with in vivo ACT risk. We detect 447 response-expression quantitative trait loci (QTLs) and 42 response-splicing QTLs, which are enriched in lower ACT GWAS [Formula: see text]-values, supporting the in vivo relevance of our map of genetic regulation of cellular response to anthracyclines.

Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.

Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic

Genome-wide association mapping for type and mammary health traits in French dairy goats identifies a pleiotropic region on chromosome 19 in the Saanen breed.

Type traits and mammary health traits are important to dairy ruminant breeding because they influence animal health, milking ability, and lo … Breeds were analyzed together and separately. The study highlighted 37 chromosome-wide significant quantitative trait loci (QTL) with linkage analyses and 222 genome-wide significant QTL for linkage disequilibrium, for type and SCC traits in dairy goats. Genomic control of those traits was mostly polygenic and breed-specific, suggesting that within-breed selection would …

Enrichment of colorectal cancer associations in functional regions: Insight for using epigenomics data in the analysis of whole genome sequence-imputed GWAS data.

BACKGROUND: The evaluation of less frequent genetic variants and their effect on complex disease pose new challenges for genomic research. To investigate whether epigenetic data can be used to inform aggregate rare-variant association methods (RVAM), we assessed whether variants more significantly associated with colorectal cancer (CRC) were preferentially located in non-coding regulatory regions, and whether enrichment was specific to colorectal tissues. METHODS: Active regulatory elements (ARE) were mapped using data from 127 tissues and cell-types from NIH Roadmap Epigenomics and Encyclope