SEARCH · PubMed Health

Results for “SNPs”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2025

Genotypes of SNPs of key genes regulate susceptibility and drug sensitivity to neovascular AMD in the human population.

OBJECTIVE: To compare the genetic characteristics of the normal control group to those of neovascular age-related macular degeneration (AMD) patients and to detect single-nucleotide polymorphisms (SNPs) related to the pathogenesis of neovascular AMD and the sensitivity to anti-VEGF drug, combercept. METHOD: This is a prospective case-controlled study. A total of 104 neovascular AMD patients were treated with combercept and 106 normal subjects were served as the control group. SNPs associated with neovascular AMD and disease susceptibility and drug sensitivity were analysed. RESULTS: Significant differences existed between neovascular AMD patients and normal subjects among genotypes of the SNPs of two genes, ARMS2 (rs10490924 T) and HTRA 1 (rs11200638 A). The T alleles in rs1065489 of CFH and the rs2230205 of C3 significantly promoted neovascular AMD in males while having no significant effect in females. Six SNPs of five genes, including C3 (rs2250656 G), CFB (rs2072633 G), CFH (rs2274700 A, rs3766405 T), KDR (rs6828477 A) and FZD 4 (rs10898563 T), had significant impact in reducing neovascular AMD. Two SNPs of the CFH gene (rs2274700 A and rs3766405 T) and one SNP of the CFB gene, rs2072633 G, were statistically significantly associated with good response to combercept. Conversely, the other two SNPs of the CFH gene, rs1065489 T and rs3753396 G, and the rs7412 T of the APOE gene were associated with a relatively poor patient response to drug action. Two sets of SNPs of CFB have a combined positive effect on disease. The two SNPs of CFH (rs1065489 T and rs3753396 G) and the combination of the two SNPs of CFH and rs7412T of APOE have negative effects on the drug effectiveness. CONCLUSIONS: These genotype differences facilitate the selection of individualised treatment options towards obtaining the most efficacious clinical treatment. These findings need to be validated by studies with different ethnic populations and/or larger samples.

Humans↗

PubMed2025

Replication and Functional Prediction of Two GWAS-Reported SNPs Located on RAD50 Gene Associated with Asthma in Pakistani Children.

BACKGROUND: Genome-wide association studies (GWAS) have indicated that several single nucleotide variants (SNVs) of the RAD50 gene are significantly associated with childhood-onset asthma. However, the biological role of RAD50, and its genomic variants that predispose individuals to asthma, remains unclear. This case-control study aimed to investigate the association of two Single nucleotide polymorphisms (SNPs) rs2244012, and rs6871536 of RAD50 with asthma susceptibility using experimental and computational tools. METHODS: The case-control study involved 355 participants: "176 asthma cases [mean age (sd) = 8.91 ±3.05] and 179 healthy controls [mean age (sd) = 11.10 ±8.86] from local Punjabi population of Pakistan. The SNPs were analyzed using a modified single base extension method. The allelic association with asthma and linkage disequilibrium (LD) between the two main SNPs were performed using the SHEsis tool. SNPStats was used to assess the association of SNPs under genotypic models and interaction with non-genetic factors. The LD calculator of ENSEMBL employed for the identification of proxy SNPs in high LD (r^2 > 0.97) to main SNPs. Additionally, HaploReg(v4.1) was utilized to gauge the impact of SNPs on genomic regulations. RESULTS: In current study, both SNPs were found to have a significant association (p-value <0.05) with childhood-onset asthma development under allelic and genotypic models. The alternative "G" allele of rs2244012 is shown to modify two regulatory motifs: Nrf-2 and Zbtb12, while the alternative "C" allele of rs6871536 is predicted to alter the OSF-2 motif. Moreover, 10 SNVs proximal to rs2244012 and 21 SNVs near rs6871536 are in high LD in the Punjabi population of Lahore, Pakistan (PJL). These proxy/high-LD SNVs also displayed the potential to change DNA regulatory motifs. CONCLUSION: the rs2244012, and rs6871536 variants of RAD50 gene are significantly association with childhood asthma in Pakistan. Despite being intronic variants, it is our inference that these two SNPs have the potential to either independently or synergistically regulate inflammatory responses via nearby SNVs.

Asthma↗

PubMed2026

Upper airway microbiome interacts with GSDMB and ORMDL3 asthma risk SNPs to influence early-life wheeze risk.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in the chromosome 17q12-q21 region and, independently, early-life nasal microbiota dominated by Moraxella, Streptococcus, or Haemophilus (MSH) increase risk of chronic wheeze and asthma development. OBJECTIVE: We sought to determine whether 17q12-q21 risk SNPs and nasal microbiota interact to modulate childhood wheeze risk. METHODS: Nasal wash samples from 12-month-old infants in 2 birth cohorts, COAST (Childhood Origins of Asthma; n = 180) and URECA (Urban Environment and Childhood Asthma; n = 139), underwent 16S ribosomal RNA variable region 4 sequencing. Nasal microbiota dominated by MSH or Corynebacterium, Dolosigranulum, Staphylococcus, or Bacillus (CDSB) were assessed. Paired blood was genotyped for 9 17q12-q21 risk SNPs. Logistic regression tested interactions between 17q12-q21 SNPs and MSH or CDSB on wheeze risk in the first 3 years of life. A549 lung epithelial cells, CRISPR-edited to encode the rs7216389 risk genotype (rs7216389TT) were compared to the heterozygous (rs7216389CT) line using bulk RNA sequencing. RESULTS: SNPs, particularly those in the ORMDL3 (rs8076131; odds ratio [OR]: 1.72; 95% CI: 1.09-2.71; Pint = .031) and GSDMB (rs2305480; OR: 1.72; 95% CI: 1.09-2.71; Pint = 0.042; and rs7216389; OR: 1.73; 95% CI: 1.09-2.70; Pint = .047) genes, interact with MSH microbiota to increase early-life wheeze risk (false discovery rate Pint = .016 for all), while interactions with CDSB reduce risk. A549 airway epithelial cells homozygous for rs7216389TT exhibited decreased expression of genes involved in antimicrobial responses and neutrophil recruitment and evidence increased microbial adherence compared with the heterozygous cell line. CONCLUSION: Airway microbiota interact with SNPs at the 17q12-q21 locus in genes involved in sphingolipid metabolism and intracellular antimicrobial responses, to modulate wheeze risk.

Humans↗

PubMed2023

Pervasive correlations between causal disease effects of proximal SNPs vary with functional annotations and implicate stabilizing selection.

The genetic architecture of human diseases and complex traits has been extensively studied, but little is known about the relationship of causal disease effect sizes between proximal SNPs, which have largely been assumed to be independent. We introduce a new method, LD SNP-pair effect correlation regression (LDSPEC), to estimate the correlation of causal disease effect sizes of derived alleles between proximal SNPs, depending on their allele frequencies, LD, and functional annotations; LDSPEC produced robust estimates in simulations across various genetic architectures. We applied LDSPEC to 70 diseases and complex traits from the UK Biobank (average N=306K), meta-analyzing results across diseases/traits. We detected significantly nonzero effect correlations for proximal SNP pairs (e.g., -0.37±0.09 for low-frequency positive-LD 0-100bp SNP pairs) that decayed with distance (e.g., -0.07±0.01 for low-frequency positive-LD 1-10kb), varied with allele frequency (e.g., -0.15±0.04 for common positive-LD 0-100bp), and varied with LD between SNPs (e.g., +0.12±0.05 for common negative-LD 0-100bp) (because we consider derived alleles, positive-LD and negative-LD SNP pairs may yield very different results). We further determined that SNP pairs with shared functions had stronger effect correlations that spanned longer genomic distances, e.g., -0.37±0.08 for low-frequency positive-LD same-gene promoter SNP pairs (average genomic distance of 47kb (due to alternative splicing)) and -0.32±0.04 for low-frequency positive-LD H3K27ac 0-1kb SNP pairs. Consequently, SNP-heritability estimates were substantially smaller than estimates of the sum of causal effect size variances across all SNPs (ratio of 0.87±0.02 across diseases/traits), particularly for certain functional annotations (e.g., 0.78±0.01 for common Super enhancer SNPs)-even though these quantities are widely assumed to be equal. We recapitulated our findings via forward simulations with an evolutionary model involving stabilizing selection, implicating the action of linkage masking, whereby haplotypes containing linked SNPs with opposite effects on disease have reduced effects on fitness and escape negative selection.

Journal Article↗

PubMed2023

Pervasive correlations between causal disease effects of proximal SNPs vary with functional annotations and implicate stabilizing selection.

Journal Article↗

PubMed2026

Correlations between causal effect sizes of proximal SNPs vary with functional annotations and implicate stabilizing selection.

Causal disease effect sizes of proximal single-nucleotide polymorphisms (SNPs) are widely assumed to be independent but could be correlated. Here we introduce a new method, linkage disequilibrium SNP-pair effect correlation regression (LDSPEC), to estimate the correlation of causal disease effect sizes of derived alleles between proximal SNPs; LDSPEC produced robust estimates in simulations. Analyzing 70 UK Biobank diseases and traits (average N = 305,646), we detected significantly non-zero SNP-pair effect correlations (for example, -0.37 ± 0.09 for low-frequency positive linkage disequilibrium 0-100-bp SNP pairs) that decayed with distance and varied with allele frequency and linkage disequilibrium between SNPs. SNP pairs with shared functions had stronger effect correlations that spanned longer genomic distances. Consequently, SNP heritability estimates were smaller than estimates of the sum of causal effect size variances across SNPs, particularly for certain functional annotations. We recapitulated our findings via forward simulations involving stabilizing selection, implicating the action of linkage masking, whereby haplotypes containing linked SNPs with opposite effects on disease have reduced effects on fitness and escape negative selection.

Polymorphism, Single Nucleotide↗

PubMed2026

Comparisons Between Large-Scale Genomic Variants and SNPs in Driving Population Divergence and Local Adaptation.

Genomic variations, such as indels (2-49 bp) and structural variants (SVs, ≥50 bp), are larger-scale mutations than single nucleotide polymorphisms (SNPs) and can substantially impact evolutionary processes, including speciation, adaptation, and phenotypes. Despite their functional importance, integrative population genetic analyses that jointly consider genome-wide SNPs, indels, and SVs remain under-explored. The ground tit (Pseudopodoces humilis), an endemic species to the Qinghai-Tibet Plateau (QTP), exhibits divergence across distinct glacial refugia, accompanied by habitat and morphological divergence, making it an excellent example for investigating how different types of genomic variants contribute to population divergence and local adaptation. Here, by retrieving 81 whole-genome sequence data, over 13 million SNPs, 2 million indels, and 22,101 SVs were identified. Variants were unevenly distributed across the genome, characterized by distinct hotspot regions. Indels and SVs revealed four genetic clusters consistent with previous SNP-based results, thereby validating the reliability of our variant datasets. FST and genotype-environment association (GEA) analyses independently revealed numerous candidate indels and SVs; each showed minimal overlap with previously identified SNPs, and were enriched in similar functional pathways such as signal transduction, skeletal muscle development, water transport, DNA repair, reproduction, nervous system development, and immunity. Collectively, our results demonstrated that indels and SVs could capture additional signatures besides SNPs. Furthermore, similar but distinct gene functions among different types of genomic variants collectively and complementarily drive genomic divergence across environmental gradients in such a high-elevation endemic species, underscoring its evolutionary relevance in local adaptation.

indels↗

PubMed2025

Construction of a Core Germplasm and Identification of Candidate SNPs Associated with Growth Performance of Epinephelus tukula by Whole-Genome Resequencing.

Epinephelus tukula is an economically important aquaculture animal, and a major parent in grouper crossbreeding. To better preserve and exploit E. tukula germplasm resources, a core collection (containing 34 individuals derived from 10 genetic groups) was first constructed based on phenotypic growth traits and whole-genome resequencing (WGS) data. The phenotypic traits of the individuals within the core collection were not significantly different from those in the original collection, suggesting effective representativeness of the core collection. Additionally, we performed genome-wide association study (GWAS) of E. tukula to identify candidate single nucleotide polymorphisms (SNPs) and genes associated with growth traits, to facilitate the improvements in the growth performance of this species. Twenty-six significant SNPs were identified, scattered among multiple chromosomes. Five SNPs were confirmed to be correlated with growth in another new group of 101 individuals. Based on the annotation results, these five SNPs were located in CCDC102A, NTRK2, CTSL, OTOF, and nestin, and were involved in cell development, differentiation and proliferation, glycolytic metabolism, neurological development, and myoblast differentiation. Our findings not only provide an effective basis for the conservation and utilization of E. tukula germplasm resources, but also promote the development of marker-assisted selection of E. tukula.

Polymorphism, Single Nucleotide↗

PubMed2025

Association of CYP19 gene SNPs (rs7176005 and rs6493497) with polycystic ovary syndrome susceptibility in Northern Chinese women.

PURPOSE: The objective of this study was to elucidate the relationship between two single nucleotide polymorphisms (SNPs) rs7176005 and rs6493497 in CYP19 gene and the risk of polycystic ovary syndrome (PCOS) in Northern Chinese women. METHODS: In this case-control study, a total of 340 women with PCOS and 340 matched healthy controls were recruited. Polymerase chain reaction ligase detection reaction (PCR-LDR) method was used to investigate two SNPs (rs7176005 and rs6493497) in the 5'-flanking region of CYP19 gene exon 1. RESULTS: We observed a significant association of rs7176005 and rs6493497 with reduced risk of PCOS. Compared with CC genotype, a significant association of CT genotype (p = 0.019), TT genotype (p < 0.001) and combined CT + TT genotype (p < 0.001) with reduced risk of PCOS was observed. The result of linkage disequilibrium analysis showed that these two SNPs are in complete linkage disequilibrium (r2 = 1). For rs7176005 SNP, compared with CC genotype, CT, TT and CT + TT genotypes reduced the risk of PCOS. The age, BMI-adjusted OR were 0.650 (95% CI = 0.460-0.917), 0.158 (95% CI = 0.066-0.376) and 0.545(95% CI = 0.391-0.759), respectively. CONCLUSIONS: These findings highlight a significant association between CYP19 gene polymorphisms and PCOS susceptibility, implying potential protective effects of T and A alleles. Of course, the major limitation of this study is the sample size of the case-control study. Larger cohort studies are needed to confirm these findings and investigate the underlying causes.

Adult↗

PubMed2011

Identification of transcriptome SNPs between Xiphophorus lines and species for assessing allele specific gene expression within F₁ interspecies hybrids.

Variations in gene expression are essential for the evolution of novel phenotypes and for speciation. Studying allelic specific gene expression (ASGE) within interspecies hybrids provides a unique opportunity to reveal underlying mechanisms of genetic variation. Using Xiphophorus interspecies hybrid fishes and high-throughput next generation sequencing technology, we were able to assess variations between two closely related vertebrate species, Xiphophorus maculatus and Xiphophorus couchianus, and their F(1) interspecies hybrids. We constructed transcriptome-wide SNP polymorphism sets between two highly inbred X. maculatus lines (JP 163 A and B), and between X. maculatus and a second species, X. couchianus. The X. maculatus JP 163 A and B parental lines have been separated in the laboratory for ≈70 years and we were able to identify SNPs at a resolution of 1 SNP per 49 kb of transcriptome. In contrast, SNP polymorphisms between X. couchianus and X. maculatus species, which diverged ≈5-10 million years ago, were identified about every 700 bp. Using 6524 transcripts with identified SNPs between the two parental species (X. maculatus and X. couchianus), we mapped RNA-seq reads to determine ASGE within F(1) interspecies hybrids. We developed an in silico X. couchianus transcriptome by replacing 90,788 SNP bases for X. maculatus transcriptome with the consensus X. couchianus SNP bases and provide evidence that this procedure overcomes read mapping biases. Employment of the in silico reference transcriptome and tolerating 5 mismatches during read mapping allow direct assessment of ASGE in the F(1) interspecies hybrids. Overall, these results show that Xiphophorus is a tractable vertebrate experimental model to investigate how genetic variations that occur during speciation may affect gene interactions and the regulation of gene expression.

Alleles↗

PubMed2025

Multivariate Effects of SNPs on Environmental Streptococcal Mastitis Evaluated With an NGS-Based Association Study Using Targeted Resequencing in the Bovine MHC Region.

Mastitis is an inflammatory reaction caused by bacterial infection of the teat, and a relationship between its onset and cattle major histocompatibility complex (BoLA) region has been reported. However, no comprehensive genetic analysis of mastitis caused by environmental streptococci has been reported. Here, we resequenced the BoLA region using a hybridisation capture target next-generation sequencing (NGS) method to identify disease susceptibility markers mapped to the BoLA region in environmental streptococcal mastitis. This study examined 75 cows with mastitis caused by environmental streptococci selected from 1641 cows with mastitis and 222 healthy cows without mastitis in Japan. Targeted sequences obtained from MiSeq NGS were aligned to the bovine reference genome (ARS-UCD1.2/bosTau9), and 2,920,355 variants were detected within the BoLA region of the 297 Holstein cattle. In an association study using 2264 variants after quality control, the top 20 variants with the lowest P values were selected and assigned to the 18 surrounding candidate genes, and a gene network analysis of these genes resulted in the narrowing down of five candidate genes POU5F1, IER3, GNL1, ABCF1, and PRR3. Multivariate effect analysis of all 6 SNPs associated with these 5 genes revealed that they were significantly correlated with mastitis, indicating that they were useful for classification of mastitis-resistant and mastitis-susceptible cattle. This is the first report to identify SNPs associated with environmental streptococcal mastitis with an NGS-based association study using targeted resequencing in the BoLA region, and understanding host factors may provide important clues for mastitis control.

Animals↗

PubMed2025

RAD-Seq-derived SNPs reveal no local population structure in the commercially important deep-sea queen snapper (Etelis oculatus) in Puerto Rico.

UNLABELLED: The queen snapper (Etelis oculatus Valenciennes in Cuvier & Valenciennes, 1828) is a deep-sea snapper whose commercial importance continues to increase in the US Caribbean. However, little is known about the biology and ecology of this species. In this study, the presence of a fine-scale population structure and genetic diversity of queen snapper from Puerto Rico was assessed through 16,188 SNPs derived from the Restriction site Associated DNA Sequencing (RAD-Seq) technique. Summary statistics estimated low genetic diversity (HO = 0.333-0.264) and did not reveal population differentiation within our samples (F ST = - 0.001-0.025). Principal component analysis and a model-based clustering method did not detect a fine-scale subpopulation structure among sampling sites, however, there was genetic variability within regions and sites. Our results have revealed comparable genetic and dispersal patterns to those observed in other shallow-water snapper species in Puerto Rico waters. It is crucial to further enhance our understanding of the ecological and biological aspect of the queen snapper to effectively manage and conserve this species as fishing pressure has been extended to deep water species in the US Caribbean. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42995-025-00289-7.

Caribbean Fisheries↗

PubMed2026

Microsatellites Versus Genome-Wide SNPs Data for Pedigree Reconstruction in Twin Simmental Crossbred Cattle.

Accurate pedigree reconstruction is critical for genetic evaluation in admixed cattle populations, yet the relative performance of microsatellite and genome-wide SNP markers in twin-rich herds with incomplete pedigree records remains unclear. We compared 12 ISAG-recommended microsatellite markers with whole-genome SNP data for dam-calf assignment in a Simmental crossbred population (n = 43, 13 dam-calf groups) from southern China. Twin zygosity was determined from SNP identity-by-descent (PI_HAT) values: nine calf pairs were dizygotic, one pair was monozygotic (20A/21A), and one adult pair was composed of dizygotic twin sisters (31A/34A). Admixture analysis at K = 3 revealed ancestry proportions of 50.7% European taurine, 28.9% Chinese indicine and 20.4% East Asian taurine. The SNP-based neighbor-joining tree correctly recovered 12 of 13 groups (92.3%, 95% CI: 64.0-99.8%), whereas the microsatellite-based tree recovered 11 (84.6%, 95% CI: 54.6-98.1%); the difference was not statistically significant (exact McNemar test, p = 1.0). Locus INRA023 was monomorphic (PIC = 0), reducing the effective number of markers to 11. These results indicate that genome-wide SNPs show a favourable trend in accuracy and are less prone to false-positive clustering than a standard microsatellite panel in admixed, twin-rich cattle populations.

SNP↗

PubMed2026

Dissecting the genetic basis underlying drought tolerance at different development stages in soybean.

INTRODUCTION: Soybean is an indispensable crop supplying protein and oil for humans and animals, and playing an essential role in global food security. Drought represses soybean seed germination, reducing biomass accumulation and even inhibiting yield. METHODS: In order to dissect the genetic components underlying soybean drought tolerance during different development stage, a natural population containing 140 accessions was employed to evaluate seven drought tolerance-related traits under water-welled and drought stress conditions. Subsequently, genome-wide association study (GWAS) was conducted based on 150K single nucleotide polymorphism (SNP) markers of "Zhongdouxin-1". And the drought tolerance coefficient of seven different traits were analyzed with seven GWAS models. RESULTS: A total of 1807 significant SNPs were detected across 20 chromosome, including 569 SNPs for germination stage, and 1242 SNPs for seedling stage. Of 569 SNPs identified in germination stage, 354 SNPs on chromosomes 2, 7, 13, 14, and 17 accounting for 62.21%. Among 1242 SNPs found in seedling stage, 869 SNPs on chromosomes 11, 14, 15, 17 and 18 accounting for 69.97%. Moreover, among 1807 significant SNPs, 163 SNPs exhibited pleiotropic effects, of which 23 were located in exon, 21 in intron, 12 in 5'UTR or 3'UTR and 11 in upstream or downstream. Furthermore, 249 stable SNPs were detected by more than four GWAS models. According to these stable SNPs, RNA expression levels and gene annotations, four causal genes (Glyma.02G080200, Glyma.11G056200, Glyma.12G188900, and Glyma.18G110200) conferring soybean drought tolerance were detected, which participated in ethylene stimulus response, water deprivation response, and proteolysis. DISCUSSION: Collectively, 249 stable SNPs, 163 pleiotropic SNPs and four candidate genes identified in present study provided promising molecular resources and reliable foundation for drought resistance improvement and marker-assisted selective breeding in soybean.

GWAS↗

PubMed2026

Associations of genetically predicted interleukin-6 and tumor necrosis factor signaling pathways with mortality among persons with colorectal cancer: a two-sample Mendelian randomization.

BACKGROUND: Despite significant progress in identifying risk factors for colorectal cancer (CRC), factors influencing survival in people with CRC remain less understood. Pro-inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) have been implicated in cancer progression and may influence CRC outcomes. We investigated associations between genetically predicted levels of IL-6 and TNF-α signaling pathways and mortality in people with CRC. METHODS: We conducted a two-sample Mendelian randomization (MR) analysis using cis-acting single nucleotide polymorphisms (SNPs) associated with soluble IL-6 receptor alpha (sIL6-RA) and IL-6 signal transducer gp130 (IL6ST), representing IL-6 signaling, and with TNF-α, and its soluble receptors (sTNF-R1, sTNF-R2). SNPs were obtained separately from two large genome-wide association studies (GWAS): deCODE and UK Biobank (UKB). The outcome was CRC-specific mortality among 16,964 CRC cases (4010 deaths) in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Analyses were stratified by tumor site and stage. The inverse variance weighted (IVW) method, incorporating a correlation matrix for dependent SNPs, was used for primary analyses. Because literature links TNF-α to CRC incidence, we additionally performed a simulation study to evaluate the potential impact of collider bias resulting from restricting analyses to CRC cases. RESULTS: Genetically predicted sIL6-RA was weakly positively associated with CRC-specific mortality (deCODE-SNPs (n = 13) HR per 1 SD increase: 1.06; 95% CI: 1.00-1.12; UKB-SNPs (n = 11) HR: 1.09; 95% CI: 1.02-1.17). Genetically proxied IL6ST levels showed no association with CRC-specific mortality in the overall sample (deCODE-SNPs (n = 19) HR: 1.04; 95% CI: 0.90-1.21; UKB-SNPs (n = 9) HR: 1.11; 95% CI: 0.87-2.42), while higher IL6ST levels were associated with increased mortality among patients with stage 2/3 disease (deCODE-SNPs (n = 19) HR: 1.45; 95% CI: 1.10-1.91; UKB-SNPs (n = 9) HR: 1.87; 95% CI: 1.22-2.89). No associations were observed for TNF-α, sTNF-R1, or sTNF-R2. Findings for all exposures were consistent across both GWAS datasets. Simulation analyses for TNF-α indicated collider bias was present but limited in magnitude. CONCLUSIONS: Our findings suggest that IL-6 signaling may play a role in CRC progression although of limited magnitude, whereas TNF-related pathways appear less relevant for prognosis.

Humans↗

PubMed2026

Identification of candidate genes for reproductive traits in Chinese Holstein cattle using single-step genome-wide association study.

In dairy farming, reproductive efficiency is vital to both profitability and sustainability. However, years of selective breeding for increased milk yield have adversely affected reproductive potential. This study aimed to pinpoint genomic regions and identify potential candidate genes associated with reproductive traits in Chinese Holstein cattle. In this study, a single-step genome-wide association study (ssGWAS) was conducted using 33,202 phenotypic records from 16,379 animals, 55,244 pedigree records, and genomic data from 1,698 cows. These data were integrated into the ssGWAS analysis, resulting in a total pedigree structure of 21,635 animals. A total of 12 significant markers were identified for calving interval (IC), days open (DO), number of services per conception (NS), and conception rate (CR). Among these significant SNPs, three SNPs were for IC, two SNPs were for DO, three SNPs were for NS, and four SNPs were for CR. Several promising candidate genes located near these SNPs have been identified, including SFXN4, B3GAT2, GRK5, PRDX3, and MTHFD1L, highlighting their potential involvement in fertility-related biological processes. Furthermore, functional enrichment analysis identified significant enrichment of pathways associated with cell adhesion and embryonic development, suggesting a potential mechanistic role for DSG family members (DSG1, DSG2, DSG3, and DSG4) in fertility regulation. Collectively, our findings enhance understanding of the complex genetic basis of reproductive traits in dairy cattle and may offer a valuable set of genomic targets for precision breeding of Chinese Holsteins. Integrating these markers into genomic selection programs may contribute to genetic improvements in reproductive efficiency and support the long-term sustainability of dairy production.

Animals↗

PubMed2025

Screening of the key single nucleotide polymorphisms in type 2 diabetes mellitus complicated with lower extremity arterial disease by machine learning.

OBJECTIVES: Diabetic lower extremity arterial disease (LEAD) is a manifestation of diabetic lower extremity vascular complications. This study aimed to screen the key single nucleotide polymorphism (SNP) gene signature in patients with type 2 diabetes mellitus (T2DM) and LEAD. METHODS: A total of 147 patients with T2DM complicated by LEAD and 144 patients with T2DM without LEAD were enrolled for transcriptome sequencing. The Plink software was used to preprocess the data. Five machine learning methods were adopted to build the SNP diagnosis models. The receiver operating characteristic (ROC) curve was used to quantify the predicted probabilities of the model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the cluster Profiler package. Finally, regression statistical analysis was used to correlate the key SNPs with clinical information and biochemical indicators. RESULTS: A total of 24 SNPs were retained and 10 SNPs were risk allele genes. Nine SNPs (rs7412, rs1800629, rs699947, rs3918242, rs668, rs1800470, rs1800449, rs1800469, and rs1024611) were identified as the key SNPs sites. GO and KEGG pathway analyses revealed that these genes are mainly enriched in fluid shear stress and atherosclerosis. Finally, rs1800449 was associated with low-density lipoprotein cholesterol (LDL-C). With high density lipoprotein cholesterol (HDL-C), related site was rs1024611. The sites associated with total cholesterol (CHOL) were rs1800449 and rs7412.The site associated with apolipoprotein B (APOB) and apolipoprotein A1 (APOA1) were rs1800470 and rs1800469. CONCLUSION: This study authenticated nine SNPs for the diagnosis of T2DM patients with LEAD, which will be of great significance in the development of diagnostic molecular biomarkers for T2DM patients.

Humans↗

PubMed2025

Identification and Validation of Novel Combinatorial Genetic Risk Factors for Endometriosis across Multiple UK and US Patient Cohorts.

BACKGROUND: Endometriosis affects about 10% of women usually of reproductive age. It often has severe negative impacts on patients' quality of life, but the average time to a definitive diagnosis remains 7-9 years, and there are few effective therapeutic options. Relatively little is known about the genetic drivers of the disease even though its heritability is fairly high. A recent large genome wide association study (GWAS) meta-analysis identified 42 genomic loci associated with risk of endometriosis, but together these explain only 5% of disease variance. METHODS: We used the PrecisionLife® combinatorial analytics platform to identify multi-SNP disease signatures significantly associated with endometriosis in a white European UK Biobank (UKB) cohort. We assessed the reproducibility of these multi-SNP disease signatures as well as 35 of the 42 meta-GWAS SNPs in a multi-ancestry American endometriosis cohort from All of Us (AoU) after controlling for population structure. RESULTS: We identified 1,709 disease signatures, comprising 2,957 unique SNPs in combinations of 2-5 SNPs, that were associated with increased prevalence of endometriosis in UKB. Pathways enriched in the disease signatures included cell adhesion, proliferation and migration, cytoskeleton remodeling, angiogenesis as well as biological processes involved in fibrosis and neuropathic pain.We observed a significant enrichment of these signatures (58-88%, p<0.04) that are also positively associated with endometriosis in the AoU cohort, including one 2-SNP signature that is individually significant. Reproducibility rates were greatest for higher frequency signatures, ranging from 80-88% for signatures with greater than 9% frequency (p<0.01) in AoU. Encouragingly, the disease signatures also show high reproducibility rates in non-white European AoU sub-cohorts (66-76%, p<0.04 for signatures with greater than 4% frequency).A total of 195 unique SNPs mapping to 98 genes were identified in the high frequency reproducing signatures (>9%). Of these, 7 genes were previously identified in the endometriosis meta-GWAS study and 16 genes have a previous association with endometriosis. 75 novel genes were identified in this study.We characterized 9 novel genes that occur at the highest frequency in reproducing signatures and that do not contain any SNPs linked to known GWAS genes, providing new evidence for links between endometriosis and autophagy and macrophage biology. Reproducibility rates, ranging between 73% to 85%. are especially strong for the signatures that contain these 9 genes independently of any SNPs mapping to the meta-GWAS genes. CONCLUSION: Although using much smaller, less well-characterized datasets than the previous whole genome meta-GWAS study, combinatorial analysis has provided important new insights into the genetics and biology of endometriosis including reproducible biologically relevant genes that are overlooked by GWAS approaches.The 75 novel gene associations provide new insights and routes for study of the disease and potential new therapies. Several of the novel genes identified are credible targets for drug discovery, repurposing and/or repositioning. Using the disease signatures identified as genetic biomarkers in trials of candidates drugs targeting specific mechanisms will enable precision medicine-based approaches. We hope this will encourage new targeted therapy discovery efforts.

Endometriosis↗