Association Studies Research Articles

Kidney multiome-based genetic scorecard reveals convergent coding and regulatory variants

Kidney dysfunction is a major cause of mortality, but its genetic architecture remains elusive. In this study, we conducted a multiancestry genome-wide association study in 2.2 million individuals and identified 1026 (97 previously unknown) independent loci. Ancestry-specific analysis indicated an attenuation of newly identified signals on common variants in European ancestry populations and the power of population diversity for further discoveries. We defined genotype effects on allele-specific gene expression and regulatory circuitries in more than 700 human kidneys and 237,000 cells. We found 1363 coding variants disrupting 782 genes, with 601 genes also targeted by regulatory variants and convergence in 161 genes. Integrating 32 types of genetic information, we present the “Kidney Disease Genetic Scorecard” for prioritizing potentially causal genes, cell types, and druggable targets for kidney disease.

Genetic and epigenetic correlation between diabetic retinopathy and polycystic ovarian syndrome: in-silico analyses-experimental research

Introduction: Metabolic disorders, such as diabetes, can give rise to complications like diabetic retinopathy and polycystic ovarian syndrome, which have emerged as a primary concern among healthcare systems. This study aims to explore the genetic and epigenetic associations between diabetic retinopathy and polycystic ovarian syndrome. Methods: Gene expression data were retrieved from the Gene Expression Omnibus database. Common genes were identified using Venn diagrams, while the Enrichment Analysis Resource database pinpointed shared signaling pathways. Additionally, shared microRNAs and circular RNAs were identified using the MiRmap and Circaintractome databases to investigate potential epigenetic links between the two conditions. Results: Analysis of datasets Gene Series Accession 53 257 and 54 248 revealed eight shared genes. These genes are involved in signaling pathways related to glycine, serine, and threonine metabolism, tRNA biosynthesis, and DNA repair. Furthermore, the genes associated with miRNA (6 cases) and circular RNAs (12 cases) were identified. These molecular factors play key roles in critical biological processes such as insulin secretion, adiponectin regulation, and electron transport in the respiratory chain. Conclusion: This study highlights the genetic, epigenetic, and metabolic pathways shared between diabetic retinopathy and polycystic ovarian syndrome, demonstrating that disruptions in these pathways may exacerbate metabolic complications. Identifying common genetic and epigenetic factors provides potential avenues for the clinical management and treatment of these disorders.

Genetic association of plasminogen activator inhibitor-1 gene polymorphisms (rs2227631 and rs6092) with susceptibility to oral premalignant disorders in a South Indian cohort.

Oral potentially malignant disorders impact the oral mucosa and elevate the risk of oral cancer. In India, the high prevalence of oral submucous fibrosis and leukoplakia is attributed to habits such as tobacco use and smoking. Plasminogen activator inhibitor-1 plays a crucial role in cancer progression. Single-nucleotide polymorphisms are the most widespread genetic variations associated with various diseases, including cancers. This study aimed to investigate the association between PAI-1 promoter rs2227631 (- 844G > A) and missense variant rs6092 (+ 43G > A) polymorphisms and the susceptibility to OSMF and leukoplakia in a South Indian cohort of chewers and smokers. The rs2227631 and rs6092 of PAI-1 were analysed using PCR- RFLP in 285 subjects including OSMF, leukoplakia and healthy controls, along with their habitual factors. The allele frequencies and genotypic associations were examined. The impact of these SNPs on mRNA secondary structure, gene-gene and protein-protein interactions was also analysed using in silico tools. The habits of chewers and smokers were (79% and 72%) in OSMF and (62% and 75%) in leukoplakia and disease prevalent was (78% and 59%) males and (22% and 26%) females respectively. The G allele of rs2227631 and A allele of rs6092 were significantly associated with the diseases (P < 0.05). PAI-1 polymorphisms rs2227631 and rs6092 were associated with OSMF and leukoplakia of the south Indian cohort.

Unraveling the Impact of Drug Metabolism on Tamoxifen Response in Breast Cancer.

The selective estrogen receptor modulator tamoxifen is a mainstay of endocrine breast cancer therapy. However, the clinical response rates of tamoxifen are inferior to those of aromatase inhibitors, which may be partially explained by variable drug exposure due to the pharmacogenetics of the drug-metabolizing enzyme cytochrome P450 (CYP) 2D6. Clinical trials investigating the association between CYP2D6 impairment and tamoxifen outcomes have yielded conflicting results. The results of a comprehensive meta-analysis of 33 single-center tamoxifen trials reported here address this inconsistency by adjusting for two biases that may affect the validity of previous association studies: allele coverage of CYP2D6 genotyping and loss of heterozygosity of the CYP2D6 locus in tumor-derived DNA. After adjustment for bias, meta-analyses show significantly reduced study heterogeneity and a higher risk of recurrence or death in patients with impaired CYP2D6 metabolism compared with those with normal activity. These data may support the use of pharmacogenetics-guided tamoxifen therapy to improve outcomes in patients with CYP2D6-compromised breast cancer. Prospective studies should be considered. See related article by MacLehose et al., p. 224.

SPAGRM: effectively controlling for sample relatedness in large-scale genome-wide association studies of longitudinal traits

SPAGRM: effectively controlling for sample relatedness in large-scale genome-wide association studies of longitudinal traits

Fecal Microbiota-based Investigations of Nitrogen Utilization Efficiency and related Traits in a Landrace x Piétrain crossbred Population.

Improving protein efficiency in pork production is a desired goal regarding resource conservation and climate protection, whereby animal breeding has great potential for sustainable improvements. Nitrogen utilization efficiency (NUE) is an important trait but laborious to measure. As blood urea nitrogen (BUN) can be used to predict NUE, it is often used as indicator trait. Both NUE and BUN were found to be heritable, however, microbial studies have not yet been carried out. The present study aimed to investigate the role of the gastrointestinal microbiota in the context of N efficiency in different fattening phases. The dataset consisted of 450 Landrace x Piétrain pigs fattened in a two-phase feeding regime. All pigs were fecal sampled and phenotyped in two fattening phases, referred to as sampling period (SP) 1 and SP2 in week 13 and week 16 post natum, respectively. Microbial communities in feces were compared across SPs and significant differences were observed. Mixed linear models were applied to quantify the microbial variance and microbiability for NUE, BUN, and related traits within each of the SPs. Except for NUE in SP1, all microbiabilities were significant and ranged from 0.079 to 0.471. Microbiome-wide association studies revealed a polymicrobial trait architecture, characterized by the contribution of many genera, with each genus having a relatively small effect on the traits. In total, four and eleven microbial genera were significantly associated with NUE and BUN, respectively. Microbial correlations were estimated between traits within SPs via bivariate analyses. Blood urea nitrogen was significantly correlated with N intake and retention in SP1 but not in SP2. Fecal microbiota composition differed significantly between SPs and the use of microbiota data across SPs resulted in a remarkable drop in microbiability for nearly all traits. This implies that microbiota data should be representative of the time point of phenotyping to fully capture microbial contribution to trait expression. The results suggest that jointly using genomic and fecal microbial data might be expedient to improve protein efficiency in fattening pigs.

Breeding of Camels in Europe: Between Continuity and Innovation

Camel breeding in Europe has undergone significant changes, intertwining historical continuity with modern innovation. Historically, dromedaries (Camelus dromedarius) and Bactrian camels (Camelus bactrianus), played essential roles in Roman logistics, medieval rituals, and agriculture, leaving archeological and cultural footprints across Europe. Following a decline during the Middle Ages, camels were largely confined to exotic collections. However, the past few decades have witnessed a resurgence in camel farming, primarily driven by tourism and the demand for camel milk, with an estimated 5000–6000 camels now present in Europe. Despite their adaptability to harsh climates and nutritional advantages, the sector faces challenges such as small population sizes, fragmented breeding efforts, and the absence of regulatory frameworks tailored to camels. Advances in genomic tools, including genome-wide association studies and SNP genotyping, have created opportunities for the genetic management of camels in Europe, yet also reveal concerns about low genetic diversity stemming from founder effects. Addressing these issues requires coordinated international efforts, standardized phenotype recording, and enhanced welfare guidelines. With climate change highlighting the resilience of camels to arid environments, their potential as sustainable livestock remains promising. This review underscores the balance between preserving the historical legacy of camels in Europe and fostering their integration into contemporary agricultural systems.

Genotyping-by-sequencing derived SNP markers reveal genetic diversity and population structure of Dactylis glomerata germplasm

Orchardgrass (Dactylis glomerata L.), a widely cultivated cool-season perennial, is an important forage crop due to its adaptability, high nutritional value, and substantial biomass. Understanding its genetic diversity and population structure is crucial for developing resilient cultivars that can withstand climate change, diseases, and resource limitations. Despite its global significance in fodder production, the genetic potential of many regional accessions remains unexplored, limiting breeding efforts. This study investigates the genetic diversity (GD) and population structure of 91 accessions of D. glomerata from Turkey and Iran using genotyping-by-sequencing based single nucleotide polymorphism (SNP) markers. A total of 2913 high-quality SNP markers revealed substantial genetic variability across provinces. Notably, accessions from Erzurum exhibited the highest GD (mean GD: 0.26; He: 0.5328), while provinces such as Bursa and Muğla demonstrated lower GD (mean GD: 0.15; He &amp;lt; 0.22), suggesting potential genetic bottlenecks. Population structure analysis using Bayesian clustering, PCoA and UPGMA dendrograms divided the accessions into three distinct clusters, with cluster membership largely reflecting geographical origins, and dry biomass content. Cluster II revealed higher GD, associated with enhanced biomass production (128 g/plant), the most important agronomic trait in forage species, supporting the notion of heterosis in breeding programs. The majority of the genetic variation (85.8%) was observed within clusters, with minimal differentiation among clusters (FST = 0.007). Genome-wide association studies (GWAS) identified significant marker-trait associations for dry biomass weight, a critical agronomic trait, with markers DArT-100715788, DArT-101043591, and DArT-101171265 and DArT-101090822 located on Chromosomes 1, 6, and 7 respectively. These findings highlight the importance of regional diversity for maintaining adaptive potential in future breeding programs.

A rare deleterious missense mutation in the AXIN2 gene in Chinese women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is an endocrine disorders and characterized by polycystic ovary morphology and oligomenorrhea, affecting fertility and health condition of female around the world. The causative factors of PCOS are complex, and genetic structure remains a long-standing medical challenge in genetics. Previous genome-wide association study (GWAS) showed that Wing-less-related integration site (Wnt) signaling is the most affected pathway among PCOS-related risk genes, and genetic mutations in the Wnt/β-catenin signaling may lead to abnormal development of PCOS. To explore the possibility of axis inhibitor-2 (AXIN2) variants in Chinese women with PCOS and assess their pathogenicities. A total of 365 Chinese women with PCOS and 905 women without PCOS as control were recruited from Jiangxi Provincial Maternal and Child Health Hospital, All of the 11 exons and flanking regions of the AXIN2 gene were amplified by polymerase chain reaction (PCR), the potential variants were analyzed by Sanger sequencing. The evolutionary conservation analysis of the identified Axin-2 mutant was analyzed among 15 vertebrates from human to zebrafish. The protein structure change was analyzed between the wild-type and mutation-type. The pathogenicity of AXIN2 variant was further analyzed in silico. We totally identified 7 genetic variants of AXIN2 in this study, including 4 synonymous and 3 missense. Among them, we find a rare deleterious missense variant [p.R714W (c.2140C > T)]. The allele frequencies of this variant were 0.82% and 0.17% in PCOS cases and matched controls, respectively. And it was ranging from 7.89e-5 to 1.47e-4 in public databases. Fisher's exact test indicated that the allele frequencies in PCOS were p < 0.05 compared to both the controls and the databases. Especially, the mutant amino acid site is highly conserved in vertebrates, while the mutation changed the 714th arginine to tryptophan resulting in significant change in the protein structural of Axin-2. In this study, we identified a rare deleterious missense AXIN2 mutation [p.R714W (c.2140C > T)] in Chinese women with PCOS, and this mutant is probably pathogenic. This study may provide a new perspective on revealing the genetic variation of PCOS.

Association Between Genetically Proxied SLC12A2 Inhibition and Inflammatory Bowel Disease: A Mendelian Randomization Study.

The global rise in hypertension prompts the use of medications to manage blood pressure. However, selecting first-line drugs remains challenging as their efficacy often stems from blood pressure reduction rather than specific pharmacological actions. Evaluating interactions between antihypertensive drugs and common diseases can aid tailored treatment. Here, we assess the potential link between antihypertensives and inflammatory bowel disease (IBD). Summary-level coronary heart disease (CHD) data (184,305 individuals), systolic BP (SBP) data (757,601 individuals), ulcerative ileocolitis data (361,188 individuals), ulcerative colitis data (364,454 individuals), other ulcerative colitis data (361,619 individuals), and ulcerative proctitis data (361,700 individuals) were all from genome-wide association studies (GWASs), FinnGen or eQTL studies publicly accessible. The DrugBank10 and ChEMBL11 databases function to identify genes encoding protein products targeted by active constituents of BP-lowering drugs. Summary-data-based MR (SMR) estimated the associations between expressions of drug target genes and symptoms of IBD. A multivariable MR study was further conducted to examine if the observed association was direct association. Subsequently, we collected blood samples from IBD patients in the Gastroenterology Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University and blood from healthy individuals at the physical examination center. Real-time quantitative PCR was employed to detect the expression changes of drug target genes in the peripheral blood of patients with IBD. Furthermore, we used Caco2 cells to construct an in vitro model of IBD, examined the expression of the target molecules, and verified the potential of Bumetanide to improve IBD. SMR analysis revealed that enhanced SLC12A2 gene expression in blood (equivalent to a one standard deviation increase) was a risk factor for ulcerative ileocolitis (beta = 0.5861, se = 0.2972, p = 0.0486) and enhanced gene expression of ACE was a protective factor. Additionally, SCNN1D and SLC16A1 played protective roles of IBD, while NR3C1 was identified as a risk factor. However, among these genes, only SLC12A2 was considered to influence the progress of inflammatory bowel disease through systolic blood pressure based on Mendelian randomization analysis results. Other genes may be associated with IBD depending on the expression of their own proteins, independent of changes in blood pressure. In the peripheral blood of IBD patients and in vitro experiments, SCL12A2 has been shown to be highly expressed in IBD. In vitro experiments have confirmed that Bumetanide can inhibit SCL12A2 to improve tight junctions, reduce inflammation levels, and ameliorate IBD symptoms. Therapeutic inhibition of SCL12A2 may benefit patients with IBD. In the future, this study may contribute to the selection of more personalized antihypertensive medications for different subgroups of hypertensive patients.

Genomics of liver abscesses in feedlot cattle.

The primary reason livers are condemned is due to abscesses, which are visible lesions detected on the liver during routine harvest of the animal. Condemned livers are deemed not fit for human consumption, and result in over $15M in lost income to the U.S. beef industry each year. Liver scoring is a 4-level measurement of abscess severity: 0 (no abscesses), A- (mild: 1-2 small abscesses), A (moderate: 2-4 active abscesses) and A+ (severe: 1 or more large, active abscesses). We quantified the degree to which known sources of variation, including genomic differences among animals, contribute to the incidence of liver abscesses in 1747 feedlot cattle fed a range of diets. Diets were grouped based on corn type (dry-rolled corn (DRC), high-moisture corn (HMC), DRC/HMC or steam-flaked Corn (SFC)) and byproduct (none, modified distillers grains plus solubles (MDGS), and Sweet Bran fed at 20%, 35% or 40%). A common set of SNP (n= 44,666) from the Illumina BovineSNP50 v2 and GGP Bovine 100K were used for genomic analyses. The posterior mean (posterior standard deviation) heritability estimate of liver score was 0.10 (0.05). Within-diet heritability estimates were not significantly different from zero but ranged from 0.02 (0.02) (MDGS) to 0.29 (0.32) (Sweet Bran fed at 35%). A BayesB Genome Wide Association Study with showed that liver score is a very polygenic trait with no large QTL segregating in this population. The genetic and phenotypic correlations of liver score with hot carcass weight, 12th rib fat, longissimus muscle area, or marbling score were not significantly different from zero. Results from the current study show that genomic selection for reduced liver score could be a useful tool to reduce the occurrence of liver abscesses in feedlot cattle, alongside current mitigation strategies; however, more data is needed to gain a better understanding of the genetic basis of liver score, as well as the relationship between liver score and other economically relevant traits, and potential genetic x diet interactions.

Causal Effect Between Gut Microbiota, Gut Bacterial Pathway, and Chronic Spontaneous Urticaria: A Large-Scale Bidirectional Mendelian Randomization Analysis.

To analyze causality between gut microbiota and chronic spontaneous urticaria (CSU) and to investigate the mediating effect of metabolic pathways. We extracted genome-wide association study summary statistics for 211 microbiota taxa from the MiBioGen consortium (N=18 340), 205 microbiota metabolic pathways from the Dutch Microbiome Project (N=7738), and CSU from the FinnGen genomics initiative (N=450). Bidirectional Mendelian randomization (MR) was performed to detect genetic causality between gut microbiota, gut bacterial pathways, and CSU. Sensitivity analyses were performed to validate the robustness of the results. Mediation MR investigated mediators in the association between gut microbiota and CSU. MR analysis suggested that the family Peptococcaceae and its child taxon, the genus Peptococcus, were risk factors for CSU. In addition, the genera Collinsella, Lachnospiraceae UCG004, Ruminococcaceae UCG004, and Sellimonas were also risk factors for CSU, whereas Family XIII UCG001, Lachnospiraceae UCG010, and Methanobrevibacter had protective effects on CSU. As for metabolic pathways, NONMEVIPP-PWY, PWY-5022, and PWY-7221 were positively associated with CSU, although others, such as KDO-NAGLIPASYN-PWY, PWY- 6353, and PWY-7400 presented a suggestive association with CSU. Moreover, PWY-7400 was a mediator in causality between the family Peptococcaceae and CSU. These results were based on nominal significance (P<.05). None of the Bonferroni corrected P values were <.05. Our study confirmed a causal association between gut microbiota and CSU, with the metabolic pathway being a potential mediator. Our findings provide new insights for further mechanistic and clinical studies in CSU.

Genome-Wide Association Study Pinpoints Novel Candidate Genes Associated with the Gestation Length of the First Parity in French Large White Sows

Gestation length (GL) is a critical indicator of reproductive performance in sows and is closely associated with other reproductive traits, such as total number born (TNB) and number born alive (NBA). Despite its importance, the genetic mechanisms underlying GL and its impact on reproductive traits remain poorly understood. In this study, we investigated the relationship between GL and reproductive traits using 7013 farrowing records and conducted an imputed whole-genome sequence-based genome-wide association study (GWAS) for GL in first-parity sows, involving 3005 French Large White sows. Our findings revealed that the heritability of GL ranged from 0.22 to 0.26. Both excessively short and long GLs were associated with negative impacts on TNB, NBA, and other reproductive traits. A total of 64 SNPs exceeded the significance threshold, leading to the identification of two novel quantitative trait loci (QTLs) on chromosome 5 (QTL-1: 15.29–15.39 Mb and QTL-2: 12.86–12.94 Mb) and three promising candidate genes: TROAP, RFX4, and ADCY6. Gene ontology and KEGG pathway enrichment analyses revealed that these candidate genes are enriched in key biological processes, including ovarian steroidogenesis, the GnRH signaling pathway, and the regulation of cAMP biosynthesis, all of which are crucial for gestation and pregnancy maintenance. These findings improve our understanding of the genetic architecture of GL in sows and offer valuable genetic markers for enhancing reproductive efficiency in breeding programs.

Massively parallel variant-to-function mapping determines functional regulatory variants of non-small cell lung cancer

Genome-wide association studies have identified thousands of genetic variants associated with non-small cell lung cancer (NSCLC), however, it is still challenging to determine the causal variants and to improve disease risk prediction. Here, we applied massively parallel reporter assays to perform NSCLC variant-to-function mapping at scale. A total of 1249 candidate variants were evaluated, and 30 potential causal variants within 12 loci were identified. Accordingly, we proposed three genetic architectures underlying NSCLC susceptibility: multiple causal variants in a single haplotype block (e.g. 4q22.1), multiple causal variants in multiple haplotype blocks (e.g. 5p15.33), and a single causal variant (e.g. 20q11.23). We developed a modified polygenic risk score using the potential causal variants from Chinese populations, improving the performance of risk prediction in 450,821 Europeans from the UK Biobank. Our findings not only augment the understanding of the genetic architecture underlying NSCLC susceptibility but also provide strategy to advance NSCLC risk stratification.

Determination of damaging SNP’s in SHANK3 gene with in silico methods

BackgroundAsperger's syndrome, autism, and other neurodevelopmental diseases are all included under the general term autism spectrum disorder. The SHANK3 gene has a significant role in autism spectrum disorder; mutations in this gene are seen in roughly 1–2% of patients with both autism and intellectual disability. This genetic association provides insight concerning SHANK3's potential significance in the disorder's development. There is considerable evidence associating SHANK3 mutations to autism spectrum disorder; hence, it is worthwhile to investigate the underlying molecular genetic mechanisms of the disease.ResultsThis research uses in silico approaches such as SIFT, PolyPhen-2, I-Mutant 2.0, and Project HOPE to find harmful SNPs, which are the single nucleotide polymorphisms the most prevalent types of genetic variation in humans, in the SHANK3 gene. After the analysis, from the NCBI dbSNP database, 1535 missense SNPs in the SHANK3 gene were identified, with 54 classified as deleterious. Among these, 30 SNPs were confirmed damaging by both SIFT and PolyPhen-2, and 28 led to increased protein stability while two decreased it. In the presented research, effects on protein structure of this SNPs are discussed.ConclusionsThis in silico study improves our understanding of the complicated molecular changes associated with the SHANK3 gene and contributes to a more comprehensive understanding of the genetic landscape. By deepening our knowledge of the genetic basis and molecular pathways linked to SHANK3 mutations, our findings may offer direction for focused experimental validations and treatment strategies for autism spectrum disorder.

Ontology-based expansion of virtual gene panels to improve diagnostic efficiency for rare genetic diseases

BackgroundVirtual Gene Panels (VGP) comprising disease-associated causal genes are utilized in the diagnosis of rare genetic diseases to evaluate candidate genes identified by whole-genome and whole-exome sequencing. VGPs generated by the PanelApp software were utilized in a UK 100,000 Genome Project pilot study to filter candidate genes, thus enhancing diagnostic efficiency for rare diseases. However, PanelApp also filtered out disease-causing genes in nearly 50% of the cases.MethodsHere, we propose various methods for optimized approach to design VGPs that significantly improve the diagnostic efficiency by leveraging the hierarchical structure of the Mondo disease ontology, without excluding disease-causing genes. We also performed computational experiments on an evaluation dataset comprising 74 patients to determine the optimal VGP design method.ResultsOur results demonstrate that the proposed method can significantly enhance rare disease diagnosis efficiency by automatically identifying candidate genes. The proposed method successfully designed VGPs that improve diagnosis efficiency without excluding disease-causing genes.ConclusionWe have developed novel methods for VGP design that leverage the hierarchical structure of the Mondo disease ontology to improve rare genetic disease diagnosis efficiency. This approach identifies candidate genes without excluding disease-causing genes, and thereby improves diagnostic efficiency.

HCNetlas: A reference database of human cell type-specific gene networks to aid disease genetic analyses.

Cell type-specific actions of disease genes add a significant layer of complexity to the genetic architecture underlying diseases, obscuring our understanding of disease mechanisms. Single-cell omics have revealed the functional roles of genes at the cellular level, identifying cell types critical for disease progression. Often, a gene impact on disease through its altered network within specific cell types, rather than mere changes in expression levels. To explore the cell type-specific roles of disease genes, we developed HCNetlas (human cell network atlas), a resource cataloging cell type-specific gene networks (CGNs) for various healthy tissue cells. We also devised 3 network analysis methods to investigate cell type-specific functions of disease genes. These methods involve comparing HCNetlas CGNs with those derived from disease-affected tissue samples. These methods find that systemic lupus erythematosus genes predominantly function in myeloid cells, and Alzheimer's disease genes mainly play roles in inhibitory and excitatory neurons. Additionally, they suggest that many lung cancer-related genes may exert their roles in immune cells. These findings suggest that HCNetlas has the potential to link disease-associated genes to cell types of action, facilitating development of cell type-resolved diagnostics and therapeutic strategies for complex human diseases.

Genome-wide association analysis and KASP markers development for protein quality traits in winter wheat

BackgroundWheat (Triticum aestivum L.) is a significant cereal crop that plays a vital role in global food production. To expedite the breeding of wheat cultivars with high protein quality, it is necessary to genetically analyze the traits related to quality. A genome-wide association study (GWAS) was conducted to identify the genomic regions responsible for protein quality traits in winter wheat.ResultsSix protein quality traits were evaluated across two locations and two years for a total of 341 wheat accessions. Utilizing the wheat 40 K SNP array, GWAS identified 97 significantly stable SNPs at 43 loci for five out of six protein quality traits using a linear mixed model. The 43 loci distribution was four for grain protein content, two for flour protein content, one for wet gluten content, four for gluten index, and thirty-two for Zeleny sedimentation value. The most significant associations were identified on chromosomes 1 A, 1B, and 1D. Haplotype analysis of loci associated with the gluten index in the 412–416 Mb interval on chromosome 1D identified three blocks. Accessions with superior haplotypes showed a significantly higher gluten index than those with inferior haplotypes. Six KASP markers were successfully developed for the gluten index, while five KASP markers were developed for the Zeleny sedimentation value. Additionally, eight candidate genes were identified that may affect protein accumulation during grain development.ConclusionsOur study identified 97 SNPs significantly associated with protein quality traits; developed 6 KASP markers for gluten index, and 5 KASP markers for Zeleny sedimentation values; screened 8 candidate genes that may be related to protein quality during grain development. Thise research will offer valuable insights for wheat breeding programs in China and globally.

Genome-wide association studies revealed genomic regions associated with production and reproduction traits in indicine cattle

Genome-wide association studies revealed genomic regions associated with production and reproduction traits in indicine cattle

Associations of four obesity indices with diabetes mellitus in Korean middle-aged and older adults using the Korean Genome and Epidemiology Study (KoGES)

BackgroundObesity is associated with a high risk of diabetes mellitus (DM); therefore, obesity-related indices are strongly associated with DM. This study evaluated the association of obesity indices, including body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and a body shape index (ABSI), with DM in Korean middle-aged and older adults.MethodsData from three population-based cohorts (Ansan and Ansung, Health Examinee, and Cardiovascular Disease Association Study, derived from the Korean Genome and Epidemiology Study) were analyzed. Logistic analysis was used to evaluate the association of BMI, WC, WHR, and ABSI with DM, after adjusting for covariates according to sex and age. The integrated discrimination index (IDI) and category-free net reclassification improvement (cfNRI) and area under the curve (AUC) of the receiver operating characteristic (ROC) curve were analyzed by age group to investigate index-specific model performance.ResultsAmong the 160,585 participants, 13,846 had DM (6,837; men [11.86%] and 7,009 women [6.81%]). Age increase was associated with an increased prevalence of DM: 2,339 (4.01%), 5,313 (8.74%), and 6,194 (14.93%) in the 40–49, 50–59, and ≥ 60 years age groups. After adjusting for covariates, the odds ratios (OR) for DM of WHR and WC were higher than those of the other indices in every age group. However, the OR for WHR, WC, and BMI decreased with age in both sexes. ABSI showed steady and slightly increasing ORs with increasing age although the ORs in both sexes were generally low for DM. For IDI and cfNRI, WHR had the highest values among all age groups. The AUC of the ROC curve showed that the WHR had the highest value in all age groups.ConclusionThe WHR had the strongest association with DM, but was not a good DM index in older people. Therefore, age-related index criteria for DM, especially in women, were needed for the effective prevention and management of DM.