Search Results (3,844)

The frequency of specific variants associated with the risk of developing cardiovascular diseases has been extensively studied through genome-wide association studies (GWASs). Differences between populations may be caused by the interaction of several factors, such as environmental and genetic backgrounds. Here, we studied 19 SNPs involved in atherosclerosis (AT) and venous thromboembolism (VTE) risk in the Azorean and mainland Portuguese populations and compared their frequencies with other European, Asian, and African populations. Results revealed that, although there was no difference between Azorean and mainland populations, eight SNPs in ADAMTS7, PCSK9, APOE, and LDLR genes showed significant statistical differences (χ², p < 0.05) when compared with the European population. The multilocus genetic profile (MGP) analysis demonstrated that 7.4% of mainlanders and 11.2% of Azoreans have a high-risk of developing atherosclerosis. The opposite tendency was observed for venous thromboembolism risk, where the mainland population presented a higher risk (6.5%) than the Azorean population (4.1%). Significant differences in VTE-MGP distribution were found among the Azorean geographic groups (p < 0.05), with the Eastern group showing the highest VTE risk. Conversely, for the risk AT-MGP, the Central group shows the highest risk (12.9%). Taken together, the data suggest a risk of developing a cardiovascular disease consistent with the European population. However, the Azorean-specific genetic background and socio-cultural habits (dietary and sedentary) may explain the differences observed, validating the need to assess the allelic and genotypic frequencies between different populations, especially in small geographical locations, such as the Azores archipelago. In conclusion, these findings can improve the prevention, diagnosis, and treatment of high-risk individuals, and contribute to reducing the lifelong burden of cardiovascular diseases in the Azorean population. Full article

Backgroud. Endometriosis is a chronic, estrogen-dependent inflammatory disease characterized by the ectopic presence of endometrial-like tissue. Although genome-wide association studies (GWAS) have identified susceptibility variants, their tissue-specific regulatory impact remains poorly understood. Objective. To functionally characterize endometriosis-associated variants by exploring their regulatory effects as expression quantitative trait loci (eQTLs) across six physiologically relevant tissues: peripheral blood, sigmoid colon, ileum, ovary, uterus, and vagina. Methods. GWAS-identified variants were cross-referenced with tissue-specific eQTL data from the GTEx v8 database. We prioritized genes either frequently regulated by eQTLs or showing the strongest regulatory effects (based on slope values, which indicate the direction and magnitude of the effect on gene expression). Functional interpretation was performed using MSigDB Hallmark gene sets and Cancer Hallmarks gene collections. Results. A tissue specificity was observed in the regulatory profiles of eQTL-associated genes. In the colon, ileum, and peripheral blood, immune and epithelial signaling genes predominated. In contrast, reproductive tissues showed the enrichment of genes involved in hormonal response, tissue remodeling, and adhesion. Key regulators such as MICB, CLDN23, and GATA4 were consistently linked to hallmark pathways, including immune evasion, angiogenesis, and proliferative signaling. Notably, a substantial subset of regulated genes was not associated with any known pathway, indicating potential novel regulatory mechanisms. Conclusions. This integrative approach highlights the com-plexity of tissue-specific gene regulation mediated by endometriosis-associated variants. Our findings provide a functional framework to prioritize candidate genes and support new mechanistic hypotheses for the molecular pathophysiology of endometriosis. Full article

Seed oil represents a key trait in soybeans, which holds substantial economic significance, contributing to roughly 60% of global oilseed production. This research employed genome-wide association mapping to identify genetic loci associated with oil content in soybean seeds. A panel comprising 341 soybean accessions, primarily sourced from Northeast China, was assessed for seed oil content at Heilongjiang Province in three replications over two growing seasons (2021 and 2023) and underwent genotyping via whole-genome resequencing, resulting in 1,048,576 high-quality SNP markers. Phenotypic analysis indicated notable variation in oil content, ranging from 11.00% to 21.77%, with an average increase of 1.73% to 2.28% across all growing regions between 2021 and 2023. A genome-wide association study (GWAS) analysis revealed 119 significant single-nucleotide polymorphism (SNP) loci associated with oil content, with a prominent cluster of 77 SNPs located on chromosome 8. Candidate gene analysis identified four key genes potentially implicated in oil content regulation, selected based on proximity to significant SNPs (≤10 kb) and functional annotation related to lipid metabolism and signal transduction. Notably, Glyma.08G123500, encoding a receptor-like kinase involved in signal transduction, contained multiple significant SNPs with PROVEAN scores ranging from deleterious (−1.633) to neutral (0.933), indicating complex functional impacts on protein function. Additional candidate genes include Glyma.08G110000 (hydroxycinnamoyl-CoA transferase), Glyma.08G117400 (PPR repeat protein), and Glyma.08G117600 (WD40 repeat protein), each showing distinct expression patterns and functional roles. Some SNP clusters were associated with increased oil content, while others correlated with decreased oil content, indicating complex genetic regulation of this trait. The findings provide molecular markers with potential for marker-assisted selection (MAS) in breeding programs aimed at increasing soybean oil content and enhancing our understanding of the genetic architecture governing this critical agricultural trait. Full article

Background: Polycystic ovary syndrome (PCOS) is a complex and multifactorial disorder affecting reproductive, endocrine, and metabolic functions in women of reproductive age. While environmental and lifestyle factors play a role, increasing evidence highlights the contribution of genetic and epigenetic mechanisms to its pathogenesis. Objective: This narrative review aims to provide an updated overview of the current evidence regarding the role of genetic variants, gene expression patterns, and epigenetic modifications in the etiopathogenesis of PCOS, with a focus on their impact on ovarian function, fertility, and systemic alterations. Methods: A comprehensive search was conducted across MEDLINE, EMBASE, PubMed, Web of Science, and the Cochrane Library using MeSH terms including “PCOS”, “Genes involved in PCOS”, and “Etiopathogenesis of PCOS” from January 2015 to June 2025. The selection process followed the SANRA quality criteria for narrative reviews. Seventeen studies published in English were included, focusing on original data regarding gene expression, polymorphisms, and epigenetic changes associated with PCOS. Results: The studies analyzed revealed a wide array of molecular alterations in PCOS, including the dysregulation of SIRT and estrogen receptor genes, altered transcriptome profiles in cumulus cells, and the involvement of long non-coding RNAs and circular RNAs in granulosa cell function and endometrial receptivity. Epigenetic mechanisms such as the DNA methylation of TGF-β1 and inflammation-related signaling pathways (e.g., TLR4/NF-κB/NLRP3) were also implicated. Some genetic variants—particularly in DENND1A, THADA, and MTNR1B—exhibit signs of positive evolutionary selection, suggesting possible ancestral adaptive roles. Conclusions: PCOS is increasingly recognized as a syndrome with a strong genetic and epigenetic background. The identification of specific molecular signatures holds promise for the development of personalized diagnostic markers and therapeutic targets. Future research should focus on large-scale genomic studies and functional validation to better understand gene–environment interactions and their influence on phenotypic variability in PCOS. Full article

Ujimqin sheep, known for its distinctive multi-vertebrae phenotypes (T13L7, T14L6, and T14L7) and economic value, has garnered significant attention. However, conventional phenotypic detection methods suffer from low efficiency and high costs. In this study, based on a key SNP locus (ABCD4 gene, Chr7:89393414, C > T) identified through a genome-wide association study (GWAS), a TaqMan-MGB (minor groove binder) genotyping system was developed. the objective was to establish a high-throughput and efficient molecular marker-assisted selection (MAS) tool. Specific primers and dual fluorescent probes were designed to optimize the reaction system. Standard plasmids were adopted to validate genotyping accuracy. A total of 152 Ujimqin sheep were subjected to TaqMan-MGB genotyping, digital radiography (DR) imaging, and Sanger sequencing. the results showed complete concordance between TaqMan-MGB and Sanger sequencing, with an overall agreement rate of 83.6% with DR imaging. For individuals with T/T genotypes (127/139), the detection accuracy reached 91.4%. This method demonstrated high specificity, simplicity, and cost-efficiency, significantly reducing the time and financial burden associated with traditional imaging-based approaches. the findings indicate that the TaqMan-MGB technique can accurately identify the T/T genotype at the SNP site and its strong association with the multi-vertebrae phenotypes, offering an effective and reliable tool for molecular breeding of Ujimqin sheep. Full article

Background: Severe damage to one side of the brain often leads to adverse consequences and can also cause widespread changes throughout the brain, especially in the contralateral area. Studying molecular changes in the contralateral cerebral hemisphere, especially with regard to genetic regulation, can help discover potential treatment strategies to promote recovery after severe brain trauma on one side. Methods: In our study, the right motor cortex was surgically removed to simulate severe unilateral brain injury, and changes in glial cells and synaptic structure in the contralateral cortex were subsequently assessed through immunohistological, morphological, and Western blot analyses. We conducted transcriptomic studies to explore changes in gene expression levels associated with the inflammatory response. Results: Seven days after corticotomy, levels of reactive astrocytes and hypertrophic microglia increased significantly in the experimental group, while synapsin-1 and PSD-95 levels in the contralateral motor cortex increased. These molecular changes are associated with structural changes, including destruction of dendritic structures and the encapsulation of astrocytes by synapses. Genome-wide transcriptome analysis showed a significant increase in gene pathways involved in inflammatory responses, synaptic activity, and nerve fiber regeneration in the contralateral cortex after corticorectomy. Key transcription factors such as NF-κB1, Rela, STAT3 and Jun were identified as potential regulators of these contralateral changes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) confirmed that the mRNA expression levels of Cacna1c, Tgfb1 and Slc2a1 genes related to STAT3, JUN, and NF-κB regulation significantly increased in the contralateral cortex of the experimental group. Conclusions: After unilateral brain damage occurs, changes in the contralateral cerebral hemisphere are closely related to processes involving inflammation and synaptic function. Full article

Background: The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) was a 3-year, multicenter, randomized controlled trial to test the effects of the MIND diet on cognitive decline in 604 individuals at risk for Alzheimer’s dementia. Here, we describe the genotyping, imputation, and quality control (QC) procedures for the genetic data of trial participants. Methods: DNA was extracted from either whole blood or serum, and genotyping was performed using the Infinium Global Diversity Array. Established sample and SNP QC procedures were applied to the genotyping data, followed by imputation using the 1000 Genomes Phase 3 v5 reference panel. Results: Significant study-site, specimen type, and batch effects were observed. A total of 494 individuals of inferred European ancestry and 58 individuals of inferred African ancestry were included in the final imputed dataset. Evaluation of the imputed APOE genotype against gold-standard sequencing data showed high concordance (98.2%). We replicated several known genetic associations identified from previous genome-wide association studies, including SNPs previously linked to adiponectin (rs16861209, p = 1.5 × 10⁻⁵), alpha-linolenic acid (rs174547, p = 1.3 × 10⁻⁷), and alpha-tocopherol (rs964184, p = 0.003). Conclusions: This dataset represents the first genetic resource derived from a dietary intervention trial focused on cognitive outcomes. It enables investigation of genetic contributions to variability in cognitive response to the MIND diet and supports integrative analyses with other omics data types to elucidate the biological mechanisms underlying cognitive decline. These efforts may ultimately inform precision nutrition strategies to promote cognitive health. Full article

The increasing demand for food to meet the needs of the planet’s growing population requires, among other factors, greater and improved meat production. Meat quality is determined by key consumer-preferred traits, particularly tenderness, juiciness, and flavor. Recently, interest has grown in analyzing the genes associated with these phenotypic characteristics. Single-nucleotide polymorphisms (SNPs) are common genomic variations in cattle and represent the most widely used molecular markers. Research on SNP variation is now a major focus of genomic studies aimed at improving meat quality. Leptin levels reflect the amount of adipose tissue in meat, also known as marbling. Several SNPs in the leptin gene and its receptor have been linked to this meat quality trait. Similarly, SNPs in the calpain/calpastatin system play a significant role in postmortem muscle proteolysis and pork tenderness. This review examines these genetic variants as markers involved in the expression of phenotypic traits in meat products and explores their mechanisms of action. Additionally, it provides insights into the genetic variants associated with production-related characteristics. Full article

The size of the gluteus medius muscle (GM) in swine significantly impacts both hindlimb conformation and carcass yield, while little is known about the genetic architecture of this trait. This study aims to estimate genetic parameters and identify candidate genes associated with this trait through a genome-wide association study (GWAS). A total of 439 commercial crossbred pigs, possessing both Landrace and Yorkshire ancestry, were genotyped using the Porcine 50K chip. The length and width of the GM were directly measured, and the area was then calculated from these values. The heritabilities were estimated by HIBLUP (V1.5.0) software, and the GWAS was conducted employing the BLINK model implemented in GAPIT3. The heritability estimates for the length, width, and area of the GM were 0.43, 0.40, and 0.46, respectively. The GWAS identified four genome-wide significant SNPs (rs81381267, rs697734475, rs81298447, and rs81458910) associated with the gluteus medius muscle area. The PDE4D gene was identified as a promising candidate gene potentially involved in the regulation of gluteus medius muscle development. Our analysis revealed moderate heritability estimates for gluteus medius muscle size traits. These findings enhance our understanding of the genetic architecture underlying porcine muscle development. Full article

This study measured eight key phenotypic traits across 259 fresh maize inbred lines, including plant height and spike length. A total of 82 single nucleotide polymorphisms (SNPs) significantly associated with these phenotypes were identified by applying a mixed linear model to calculate the best linear unbiased prediction (BLUP) values and integrating genome-wide genotypic data through genome-wide association analysis (GWAS). A further analysis of significant SNPs contributed to the identification of 63 candidate genes with functional annotations. Notably, 11 major candidate genes were identified from multi-trait association loci, all of which exhibited highly significant P-values (<0.0001) and explained between 7.21% and 12.78% of phenotypic variation. These 11 genes, located on chromosomes 1, 3, 4, 5, 6, and 9, were functionally involved in signaling, metabolic regulation, structural maintenance, and stress response, and are likely to play crucial roles in the growth and physiological processes of fresh maize inbred lines. The functional genes identified in this study have significant implications for the development of molecular markers, the optimization of breeding strategies, and the enhancement of quality in fresh maize. Full article

Vegetable oils are essential for human nutrition and industrial applications. With growing global demand, increasing oil content in oilseed crops has become a top priority. This review synthesizes recent progress in understanding the genetic, environmental, and molecular mechanisms regulating oil content, and presents biotechnological strategies to enhance oil accumulation in major oilseed crops. Oil biosynthesis is governed by intricate genetic–environmental interactions. Environmental factors and agronomic practices significantly impact oil accumulation dynamics. Quantitative trait loci (QTL) mapping and genome-wide association studies (GWAS) have identified key loci and candidate genes involved in lipid biosynthesis pathways. Transcription factors and epigenetic regulators further fine-tune oil accumulation. Biotechnological approaches, including marker-assisted selection (MAS) and CRISPR/Cas9-mediated genome editing, have successfully generated high-oil-content variants. Future research should integrate multi-omics data, leverage AI-based predictive breeding, and apply precision genome editing to optimize oil yield while maintaining seed quality. This review provides critical references for the genetic improvement and breeding of high- and ultra-high-oil-content varieties in oilseed crops. Full article

Climate change is jeopardizing global food security, with at least 713 million people facing hunger. To face this challenge, legumes as common beans could offer a nature-based solution, sourcing nutrients and dietary fiber, especially for rural communities in Latin America and Africa. However, since common beans are generally heat and drought susceptible, it is imperative to speed up their molecular introgressive adaptive breeding so that they can be cultivated in regions affected by extreme weather. Therefore, this study aimed to couple an advanced panel of common bean (Phaseolus vulgaris L.) × tolerant Tepary bean (P. acutifolius A. Gray) interspecific lines with Bayesian regression algorithms to forecast adaptation to the humid and dry sub-regions at the Caribbean coast of Colombia, where the common bean typically exhibits maladaptation to extreme heat waves. A total of 87 advanced lines with hybrid ancestries were successfully bred, surpassing the interspecific incompatibilities. This hybrid panel was genotyped by sequencing (GBS), leading to the discovery of 15,645 single-nucleotide polymorphism (SNP) markers. Three yield components (yield per plant, and number of seeds and pods) and two biomass variables (vegetative and seed biomass) were recorded for each genotype and inputted in several Bayesian regression models to identify the top genotypes with the best genetic breeding values across three localities on the Colombian coast. We comparatively analyzed several regression approaches, and the model with the best performance for all traits and localities was BayesC. Also, we compared the utilization of all markers and only those determined as associated by a priori genome-wide association studies (GWAS) models. Better prediction ability with the complete SNP set was indicative of missing heritability as part of GWAS reconstructions. Furthermore, optimal SNP sets per trait and locality were determined as per the top 500 most explicative markers according to their β regression effects. These 500 SNPs, on average, overlapped in 5.24% across localities, which reinforced the locality-dependent nature of polygenic adaptation. Finally, we retrieved the genomic estimated breeding values (GEBVs) and selected the top 10 genotypes for each trait and locality as part of a recommendation scheme targeting narrow adaption in the Caribbean. After validation in field conditions and for screening stability, candidate genotypes and SNPs may be used in further introgressive breeding cycles for adaptation. Full article

Background: In recent years, comprehensive analyses using a genome-wide association study (GWAS) have been conducted to identify genetic factors related to athletic performance. In this study, we investigated the association between genetic variants and elite wrestling status across multiple ethnic groups using a genome-wide genotyping approach. Methods: This study included 168 elite wrestlers (64 Japanese, 67 Turkish, and 36 Russian), all of whom had competed in international tournaments, including the Olympic Games. Control groups consisted of 306 Japanese, 137 Turkish, and 173 Russian individuals without elite athletic backgrounds. We performed a GWAS comparing allele frequencies of single-nucleotide polymorphisms (SNPs) between elite wrestlers and controls in each ethnic cohort. Cross-population analysis comprised (1) identifying SNPs with nominal significance (p < 0.05) in all three groups, then (2) meta-analyzing overlapped SNPs to assess effect consistency and combined significance. Finally, we investigated whether the most significant SNPs were associated with gene expression in skeletal muscle in 23 physically active men. Results: The GWAS identified 328,388 (Japanese), 23,932 (Turkish), and 30,385 (Russian) SNPs reaching nominal significance. Meta-analysis revealed that the ATP2A3 rs6502758 and UNC5C rs265061 polymorphisms were associated (p < 0.0001) with elite wrestling status across all three populations. Both variants are located in intronic regions and influence the expression of their respective genes in skeletal muscle. Conclusions: This is the first study to investigate gene polymorphisms associated with elite wrestling status in a multi-ethnic cohort. ATP2A3 rs6502758 and UNC5C rs265061 polymorphisms may represent important genetic factors associated with achieving an elite status in wrestling, irrespective of ethnicity. Full article

Conventional methods for generating knock-out or knock-in mammalian cell models using CRISPR-Cas9 genome editing often require tedious single-cell clone selection and expansion. In this study, we develop and optimise rapid and robust strategies to engineer homozygous fluorescent reporter knock-in cell pools with precise genome editing, circumventing clonal variability inherent to traditional approaches. To reduce false-positive cells associated with random integration, we optimise the design of donor DNA by removing the start codon of the fluorescent reporter and incorporating a self-cleaving T2A peptide system. Using fluorescence-assisted cell sorting (FACS), we efficiently identify and isolate the desired homozygous fluorescent knock-in clones, establishing stable cell pools that preserve parental cell line heterogeneity and faithfully reflect endogenous transcriptional regulation of the target gene. We evaluate the knock-in efficiency and rate of undesired random integration in the electroporation method with either a dual-plasmid system (sgRNA and donor DNA in two separate vectors) or a single-plasmid system (sgRNA and donor DNA combined in one vector). We further demonstrate that coupling our single-plasmid construct with an integrase-deficient lentivirus vector (IDLV) packaging system efficiently generates fluorescent knock-in reporter cell pools, offering flexibility between electroporation and lentivirus transduction methods. Notably, compared to the electroporation methods, the IDLV system significantly minimises random integration. Moreover, the resulting reporter cell lines are compatible with most of the available genome-wide sgRNA libraries, enabling unbiased CRISPR screens to identify key transcriptional regulators of a gene of interest. Overall, our methodologies provide a powerful genetic tool for rapid and robust generation of fluorescent reporter knock-in cell pools with precise genome editing by CRISPR-Cas9 for various research purposes. Full article

Background: Rheumatoid arthritis (RA) is an autoimmune disease that remains incurable. An increasing number of proteomic genome-wide association studies (GWASs) are emerging, offering immense potential for identifying novel therapeutic targets for diseases. This study aims to identify potential therapeutic targets for RA based on human plasma proteome. Methods: Protein quantitative trait loci were extracted and integrated from eight large-scale proteomic GWASs. Proteome-wide Mendelian randomization (Pro-MR) was performed to prioritize proteins causally associated with RA. Further validation of the reliability and stratification of prioritized proteins was performed using MR meta-analysis, colocalization, and transcriptome-wide summary-data-based MR. Subsequently, prioritized proteins were characterized through protein–protein interaction and enrichment analyses, pleiotropy assessment, genetically engineered mouse models, cell-type-specific expression analysis, and druggability evaluation. Phenotypic expansion analyses were also conducted to explore the effects of the prioritized proteins on phenotypes such as endocrine disorders, cardiovascular diseases, and other immune-related diseases. Results: Pro-MR prioritized 32 unique proteins associated with RA risk. After validation, prioritized proteins were stratified into four reliability tiers. Prioritized proteins showed interactions with established RA drug targets and were enriched in an immune-related functional profile. Four trans-associated proteins exhibited vertical or horizontal pleiotropy with specific genes or proteins. Genetically engineered mouse models for 18 prioritized protein-coding genes displayed abnormal immune phenotypes. Single-cell RNA sequencing data were used to validate the enriched expression of several prioritized proteins in specific synovial cell types. Nine prioritized proteins were identified as targets of existing drugs in clinical trials or were already approved. Further phenome-wide MR and mediation analyses revealed the effects and potential mediating roles of some prioritized proteins on other phenotypes. Conclusions: This study identified 32 plasma proteins as potential therapeutic targets for RA, expanding the prospects for drug discovery and deepening insights into RA pathogenesis. Full article