SEARCH · Search PubMed

Results for “genome-wide association study”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

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

At least 37 records · Page 2Linked to original sources

PubMed2025

A genome-wide association study of methamphetamine use among people with HIV.

BACKGROUND: Amphetamine-like stimulants are the most used psychostimulants in the world; methamphetamine use is the most prevalent in people with HIV. Prolonged methamphetamine use can cause lasting damage to the heart, gut, and brain, as well as auditory hallucinations and paranoid thinking. However, relatively little is known about methamphetamine use and its genetic contributors. METHODS: Using genetic information from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort, we conducted a multi-ancestry genome-wide association study (GWAS) of methamphetamine use among people with HIV (n = 1,196 reported ever use, n = 4,750 reported never use). RESULTS: No single nucleotide polymorphism was statistically associated with methamphetamine use at the genome-wide level (p < 5 * 10-8) in our study. Further, we did not replicate previously suggested genetic variants from other studies (all p > 0.05 in our analysis). DISCUSSION: Our study suggests that there is no single strong genetic contributor to lifetime use of methamphetamine in people with HIV enrolled in CNICS. Larger studies with more refined outcome assessment are warranted to further understand the contribution of genetics to methamphetamine use and use disorder. Investigation into social and environmental contributors to methamphetamine use are similarly necessary.

Humans↗

PubMed2024

Genome-Wide Association Study of Accessory Atrioventricular Pathways.

IMPORTANCE: Understanding of the genetics of accessory atrioventricular pathways (APs) and affiliated arrhythmias is limited. OBJECTIVE: To investigate the genetics of APs and affiliated arrhythmias. DESIGN, SETTING, AND PARTICIPANTS: This was a genome-wide association study (GWAS) of APs, defined by International Classification of Diseases (ICD) codes and/or confirmed by electrophysiology (EP) study. Genome-wide significant AP variants were tested for association with AP-affiliated arrhythmias: paroxysmal supraventricular tachycardia (PSVT), atrial fibrillation (AF), ventricular tachycardia, and cardiac arrest. AP variants were also tested in data on other heart diseases and measures of cardiac physiology. Individuals with APs and control individuals from Iceland (deCODE Genetics), Denmark (Copenhagen Hospital Biobank, Danish Blood Donor Study, and SupraGen/the Danish General Suburban Population Study [GESUS]), the US (Intermountain Healthcare), and the United Kingdom (UK Biobank) were included. Time of phenotype data collection ranged from January 1983 to December 2022. Data were analyzed from August 2022 to January 2024. EXPOSURES: Sequence variants. MAIN OUTCOMES AND MEASURES: Genome-wide significant association of sequence variants with APs. RESULTS: The GWAS included 2310 individuals with APs (median [IQR] age, 43 [28-57] years; 1252 [54.2%] male and 1058 [45.8%] female) and 1 206 977 control individuals (median [IQR] year of birth, 1955 [1945-1970]; 632 888 [52.4%] female and 574 089 [47.6%] male). Of the individuals with APs, 909 had been confirmed in EP study. Three common missense variants were associated with APs, in the genes CCDC141 (p.Arg935Trp: adjusted odds ratio [aOR], 1.37; 95% CI, 1.24-1.52, and p.Ala141Val: aOR, 1.55; 95% CI 1.34-1.80) and SCN10A (p.Ala1073Val: OR, 1.22; 95% CI, 1.15-1.30). The 3 variants associated with PSVT and the SCN10A variant associated with AF, supporting an effect on AP-affiliated arrhythmias. All 3 AP risk alleles were associated with higher heart rate and shorter PR interval, and have reported associations with chronotropic response. CONCLUSIONS AND RELEVANCE: Associations were found between sequence variants and APs that were also associated with risk of PSVT, and thus likely atrioventricular reentrant tachycardia, but had allele-specific associations with AF and conduction disorders. Genetic variation in the modulation of heart rate, chronotropic response, and atrial or atrioventricular node conduction velocity may play a role in the risk of AP-affiliated arrhythmias. Further research into CCDC141 could provide insights for antiarrhythmic therapeutic targeting in the presence of an AP.

Humans↗

PubMed2026

Genome-wide association studies for feed efficiency, production and feeding behavior traits in Canadian purebred Duroc pigs.

This study aimed to identify potential genetic variants and candidate genes associated with feed efficiency (FE), production, and feeding behavior traits in Canadian purebred Duroc pigs. Genome-wide association studies (GWAS) were conducted using 8,861 individuals and an imputed Affymetrix PigGen Canada 50K panel v2.0 using a linear mixed model (LMM) and a Bayesian B model. This analysis used an adjusted P-value threshold (ranging from 6.6 × 10-5 to 1.3 × 10-4) using a false-discovery rate to determine significance. The number of significant SNPs identified for each trait was as follows: average daily gain (ADG, 48), daily feed intake (DFI, 85), feed conversion ratio (FCR, 101), residual feed intake (RFI, 37), residual gain (RG, 64), residual intake and gain (RIG, 55), backfat thickness (BF, 100), loin depth (LD, 6), Kleiber's ratio (KR, 0), total time spent eating per day (TPD, 7), and number of visits to the feeder per day (NVD, 6). Several traits (BF, DFI, FCR, RFI, RG, and RIG) showed strong overlapping signals on chromosomes 7 and 10 with 24 shared significant SNPs, indicating potential shared genetic mechanisms. These traits also had 71 overlapping candidate genes, such as PACSIN1, PTCH1, ADIPOR1, and ITPR3, associated with glucose, lipid, and cholesterol metabolism. Well-known candidate genes in literature associated with growth and fatness such as MC4R and CDH20 were also identified to be associated with ADG, BF, FCR, and DFI in this study. Gene ontology enrichment analysis revealed that a set of the candidate genes were involved in the gonadotropin-releasing hormone (GnRH) and the platelet-derived growth factor (PDGF) signaling pathways. Overall, this study contributed to understanding the genetic architecture and provided a biological foundation for improving FE, production, and feeding behavior traits in Canadian Duroc pigs, facilitating the selection of more efficient pigs.

Sus scrofa↗

PubMed2025

A genome-wide association study of stroke risk in Asian statin users: evidence from KoGES and UK Biobank.

BACKGROUND: Despite proven efficacy of statins in stroke prevention, genetic factors may influence individual stroke risk among statin users. With increasing precision medicine approaches and growing evidence of population-specific genetic variations, identifying genetic markers that predict stroke risk in statin-treated Asian populations has become critically important for personalized cardiovascular prevention strategies. METHODS: We conducted a genome-wide association study of 1,678 participants using lipid-lowering agents in the Korean Genome and Epidemiology Study (KoGES) cohort. Significant findings were replicated in 2,170 Asian participants on statins from the UK Biobank using an additive genetic model adjusted for relevant covariates. RESULTS: In the discovery analysis, 83 single nucleotide polymorphisms were suggestively associated with stroke (p <1.0 × 10-5). Among these, 21 SNPs in the CDH13 gene were associated with increased stroke risk. The lead SNP, rs7201829, was significantly replicated in the UK Biobank (odds ratio: 2.29, p = 2.39 × 10-5). CONCLUSIONS: This study identified CDH13 as a significant genetic marker associated with stroke risk among Asian statin users. These findings provide the first genome-wide evidence for genetic determinants of stroke susceptibility during statin therapy, supporting the development of personalized prevention strategies in Asian populations.

Aged↗

PubMed2026

Analyzing salinity tolerance in grass carp (Ctenopharyngodon idella): Insights from genome-wide association study and genomic selection.

Grass carp (Ctenopharyngodon idella) is one of the most widely cultured freshwater fish species globally. However, the expansion of its farming scale faces severe limitation owing to freshwater scarcity; therefore, the development of strains with greater salinity tolerance is key for expanding production using brackish water resources. To investigate the genetic basis of salinity tolerance in grass carp, a genome-wide association study (GWAS) was conducted using 200 individuals representing extreme phenotypes, namely salinity-tolerant and salinity-sensitive groups. In total, 17 single nucleotide polymorphisms (SNPs) related to salinity tolerance were detected, which were distributed across 11 chromosomes. Through gene annotation, 38 candidate genes were obtained from these loci. Enrichment analysis revealed these candidate genes are primarily implicated in key biological processes, including osmotic regulation, energy metabolism, and stress responses. Analyses of different SNP densities revealed that the 5 K SNP density panel can balance prediction accuracy and computational efficiency. The BayesA model achieved the highest prediction accuracy under the GWAS_Evenly selection strategy, with substantial reductions in mean absolute error and mean square error. This study reveals the genetic mechanisms of salinity tolerance in grass carp, which might be optimized through genomic selection, and provides insights for selectively breeding new varieties with greater salinity tolerance.

Animals↗

PubMed2024

Genome-wide association studies with experimental validation identify a protective role for B lymphocytes against chronic post-surgical pain.

BACKGROUND: Chronic post-surgical pain (CPSP) significantly impacts patients' recovery and quality of life. Although environmental risk factors are well-established, genetic risk remains less understood. METHODS: A meta-analysis of genome-wide association studies followed by partitioned heritability was performed on 1350 individuals across five surgery types: hysterectomy, mastectomy, abdominal, hernia, and knee. In subsequent animal studies, withdrawal thresholds to evoked mechanical stimulation were measured in Rag1 null mutant and wild-type mice after plantar incision and laparotomy. Cell sorting by flow cytometry tracked recruitment of immune cell types. RESULTS: We discovered 77 genome-wide significant single-nucleotide polymorphism (SNP) hits, distributed among 24 loci and 244 genes. Meta-analysis of all cohorts estimated a SNP-based narrow-sense heritability for CPSP at ∼39%, indicating a substantial genetic contribution. Partitioned heritability analysis across a wide variety of tissues revealed enrichment of heritability in immune system-related genes, particularly those associated with B and T cells. Rag1 null mutant mice lacking both T and B cells exhibited exacerbated and prolonged allodynia up to 42 days after surgery, which was rescued by B-cell transfer. Recruitment patterns of B cells but not T cells differed significantly during the first 7 days after injury in the footpad, lymph nodes, and dorsal root ganglia. CONCLUSIONS: These findings suggest a key protective role for the adaptive immune system in the development of chronic post-surgical pain.

Animals↗

PubMed2025

Cross-Phenotype Genome-Wide Association Study on the Shared Genetic Susceptibility to Systemic Sclerosis and Primary Biliary Cholangitis.

OBJECTIVE: An increased risk of primary biliary cholangitis (PBC) has been reported in patients with systemic sclerosis (SSc). Our study aims to investigate the shared genetic susceptibility between the two disorders and to define candidate causal genes using cross-phenotype genome-wide association study (GWAS) meta-analysis. METHODS: We performed cross-phenotype GWAS meta-analysis and Bayesian colocalization analysis for patients with SSc and patients with PBC. We performed both genome-wide and locus-based analysis, including tissue and pathway enrichment analyses, fine-mapping, Bayesian colocalization analyses with expression quantitative trait loci and protein quantitative trait loci (pQTL) datasets, and phenome-wide association studies. Finally, we used an integrative approach to prioritize candidate causal genes from the novel loci. RESULTS: We detected a strong genetic correlation between SSc and PBC (global genetic correlation = 0.84, P = 1.7 × 10-6). In the cross-phenotype GWAS meta-analysis, we identified 44 nonhuman leukocyte antigens loci that reached genome-wide significance (P < 5 × 10-8). Evidence of shared causal variants between patients with SSc and patients with PBC was found for nine loci, five of which were novel. Integrating multiple sources of evidence, we prioritized CD40, ERAP1, PLD4, SPPL3, and CCDC113 as novel candidate causal genes. The CD40 risk locus colocalized with trans-pQTLs of multiple plasma proteins involved in B cell function. CONCLUSION: Our study supports a strong shared genetic susceptibility between SSc and PBC. Using cross-phenotype analyses, we have prioritized several novel candidate causal genes and pathways for these disorders.

Humans↗

PubMed2026

Disentangling Sex Differences in Sulfonylurea Drug Response With Genome-Wide Association Studies in Individuals With Type 2 Diabetes.

Sulfonylureas are a cornerstone of type 2 diabetes therapy despite interindividual variability in response. Despite well-documented sex-based differences, pharmacogenomic and genome-wide association studies (GWAS) have largely overlooked sex as a biological variable. We conducted the first sex-stratified GWAS of hemoglobin A1c (HbA1c) response to sulfonylureas in Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial participants (N = 871). Variants meeting genome-wide (P < 5.0 × 10-8) and suggestive (P < 5.0 × 10-6) significance were assessed for replication in the Pharmacogenomics of Metformin (PMET1) cohort. Replicated variants were further analyzed in the Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH) cohort to assess acute insulin and glucose responses to a single glipizide dose. Genome-wide significant loci with sex-specific effects were identified: KAZN, KIF2B, SLC39A10, and SPINK5 (combined-sex); CRACR2A, KCNK2, and TENM2 (male-only); and NACPH2 (female-only). Two suggestive variants in the TMEM64/NECAB1 locus, associated with reduced HbA1c response to sulfonylureas in the male-only ACCORD analysis, were directly replicated in the PMET1 male-only cohort. In SUGAR-MGH, one replicated variant (rs6471250-C) was significantly associated with reduced peak insulin in males (P = 0.035) but not females (P = 0.40), demonstrating sex-specific functional effects. This study identified statistically supported and biologically plausible loci with prior evidence linking nearby genes to pathways relevant to sulfonylurea action, including insulin secretion, insulin regulation/sensitivity, calcium signaling, potassium-channel biology, and glucose transport. The findings highlight sex-specific differences in sulfonylurea response, providing mechanistic insights and underscoring the importance of sex-specific precision medicine. Identification of genetic variants influencing sex-specific response could inform dosing to optimize sulfonylureas.

Humans↗

PubMed2025

A genome-wide association study identifies a novel East Asian-specific locus for dementia with Lewy bodies in Japanese subjects.

BACKGROUND: Dementia with Lewy bodies (DLB) is the second most common type of degenerative dementia in older patients. As with other multifactorial diseases, the pathogenesis results from interactions of environmental and genetic factors. The genetic basis of DLB is not yet fully understood. Recent genomic analyses of DLB in Caucasian cohorts identified genetic susceptibility loci for DLB, but the comprehensive genomic analysis in Asians was still not performed. METHODS: We conducted a genome-wide association study (GWAS) in Japanese subjects (211 DLB cases and 6113 controls) to clarify the genetic architecture of DLB pathogenesis. RESULTS: We identified the East Asian-specific DHTKD1 locus (rs138587229) on chromosome 10 with genome-wide significance (GWS; P = 3.2710-8) and the ICOS/PARD3B locus on chromosome 2 with suggestive significance (P = 3.9510-7) as novel DLB genetic risk loci. We also confirmed the APOE locus (rs429358, P < 5.0 × 10-8), a known risk locus for DLB and Alzheimer's disease in Caucasians. The DHTKD1 locus was associated with the gene expression of SEC61A2 and showed a causal relationship with cholinesterase levels. In a trans-ethnic meta-analysis that included Japanese, UK Biobank, and other Caucasian GWAS, we confirmed the risk for DLB at APOE and SNCA loci with GWS. Transcriptome-wide association analysis identified ZNF155 and ZNF284 in the brain cortex and GPRIN3 in the substantia nigra as putative causal genes for DLB. CONCLUSIONS: This is the first GWAS for DLB in East Asians, and our findings provide new biological and clinical insights into the pathogenesis of DLB.

Aged↗

PubMed2026

Consensus meta-analysis of genome-wide association studies for Alzheimer's disease and related dementias.

To better characterize the genetic architecture underlying Alzheimer's disease (AD) and related dementias (ADRD), we performed a meta-analysis of European-ancestry genome-wide association studies in 128,681 cases or proxy cases of ADRD and 849,833 (proxy) controls. We identified 91 genetic loci associated with ADRD risk, of which 16 are new and 56 are specifically detected in clinically diagnosed AD cases. We also provide a list of 18 loci (15 new) requiring further external validation. A polygenic score combining the effects of ADRD loci other than APOE was primarily associated with AD rather than non-AD pathology. Individuals in the tenth decile of the score exhibited a twofold increased risk of presenting with Braak neurofibrillary tangles stage of >4 and moderate-to-severe neuritic amyloid plaque pathology at death compared to individuals in the median score group. In conclusion, our study validated a large number of loci associated with the risk of clinically diagnosed AD, while further investigations are required to confirm the impact of the other loci on AD clinical diagnosis and of each locus on AD pathology.

Humans↗

PubMed2025

Genome-wide association studies in chronic venous disease: A systematic review.

BACKGROUND: Chronic venous disease (CVD) arises from venous hypertension secondary to impaired venous return, causing significant morbidity and diminished quality of life. Genetic factors are likely important in the pathogenesis and susceptibility of a patient to develop CVD. This systematic review summarizes genome-wide association studies (GWASs) that investigate the link between genetic variants and CVD. METHODS: A systematic review was conducted in accordance with the PRISMA guidelines, with the search dates ranging from January 1, 1994, to July 17, 2025. Abstract and full-text screening were completed by two independent reviewers, with any conflicts referred to a third senior reviewer. GWASs in adults investigating links between genetic variants and CVD were included. Exclusion criteria included patients with venous thromboembolism, arterial or diabetic disease, or animal models. RESULTS: Thirteen studies were included after screening 517 studies from a search of PubMed, EMBASE, and Ovid. Database sources included UK Biobank, FinnGen, PopGen, and country- or hospital-specific databases with a majority Caucasian and European patient cohort. A total of 602,760 patients were identified with varicose veins and 3,664,604 control cases that were studied with GWASs and other statistical methods including a two-sample Mendelian randomization approach, functional mapping, and genetic correlations. A variety of statistically significant genetic polymorphisms were identified that can be attributed to the heritability of varicose veins affecting inflammation and immunity (eg, PPP3R1, EBF1, and GATA2), hypertension (eg, CASZ1), and vascular architecture (eg, CASZ1, PIEZO1, and STIM2). Protective variants (eg, GJD3, MMP10, and 4EBP1) were also identified in Finnish populations. However, replication studies showed that these genetic polymorphisms are not generalizable to specific populations. CONCLUSIONS: This systematic review highlights genes contributing to the development of CVD that have been identified in the literature. An improved understanding of genetic contributions to the pathogenesis of CVD may inform future diagnostics, prognostics, and personalized treatment. Further larger scale studies representative of global populations, including meta-analyses of genome-wide association datasets, are required owing to individual GWASs being statistically insufficient to draw generalizable conclusions.

Humans↗

PubMed2025

A genome-wide association study identified 10 novel genomic loci associated with intrinsic capacity.

BACKGROUND: Intrinsic capacity (IC) is a multidimensional concept within the World Health Organization framework for healthy aging. It refers to the composite of an individual's physical and mental capacities that enable them to maintain well-being, functional ability, and engagement in valued activities throughout life. While substantial evidence supports the biological basis of IC and its subdomains, the extent to which genetic factors influence IC remains largely unexplored, with no studies currently available. METHODS: Using datasets from the UK Biobank (UKB; N = 44 631) and the Canadian Longitudinal Study on Aging (CLSA; N = 13 085), we implemented the restricted maximum likelihood method to estimate SNP-based heritability (h2snp), followed by a Genome-Wide Association Study (GWAS) to identify genetic variants associated with IC, and post-GWAS analyses to pinpoint biological implications. RESULTS: The h2snp for IC was estimated at 25.2% in UKB and 19.5% in CLSA. Our GWAS identified 38 independent SNPs for IC across 10 genomic loci and 4289 candidate SNPs, mapped to 197 genes. Post-GWAS analysis revealed the role of these genes in cellular processes such as cell proliferation, immune function, metabolism, and neurodegeneration, with high expression in muscle, heart, brain, adipose, and nerve tissues. Of the 52 traits tested, 23 showed significant genetic correlations with IC, and a higher genetic loading for IC was associated with higher IC scores. CONCLUSIONS: Overall, this study provides comprehensive evidence on the genetic architecture of IC, identifying novel genetic variants and biological pathways, advancing our current knowledge and laying the foundation for ongoing and future research on healthy aging.

Adult↗

PubMed2024

Genomic prediction and genome-wide association studies of morphological traits and distraction index in Korean Sapsaree dogs.

The Korean Sapsaree dog is a native breed known for its distinctive appearance and historical significance in Korean culture. The accurate estimation of breeding values is essential for the genetic improvement and conservation of such indigenous breeds. This study aimed to evaluate the accuracy of breeding values for body height, body length, chest width, hair length, and distraction index (DI) traits in Korean Sapsaree dogs. Additionally, a genome-wide association study (GWAS) was conducted to identify the genomic regions and nearby candidate genes influencing these traits. Phenotypic data were collected from 378 Korean Sapsaree dogs, and of these, 234 individuals were genotyped using the 170k Illumina CanineHD BeadChip. The accuracy of genomic predictions was evaluated using the traditional BLUP method with phenotypes only on genotyped animals (PBLUP-G), another traditional BLUP method using a pedigree-based relationship matrix (PBLUP) for all individuals, a GBLUP method based on a genomic relationship matrix, and a single-step GBLUP (ssGBLUP) method. Heritability estimates for body height, body length, chest width, hair length, and DI were 0.45, 0.39, 0.32, 0.55, and 0.50, respectively. Accuracy values varied across methods, with ranges of 0.22 to 0.31 for PBLUP-G, 0.30 to 0.57 for PBLUP, 0.31 to 0.54 for GBLUP, and 0.39 to 0.67 for ssGBLUP. Through GWAS, 194 genome-wide significant SNPs associated with studied Sapsaree traits were identified. The selection of the most promising candidate genes was based on gene ontology (GO) terms and functions previously identified to influence traits. Notable genes included CCKAR and DCAF16 for body height, PDZRN3 and CNTN1 for body length, TRIM63, KDELR2, and SUPT3H for chest width, RSPO2, EIF3E, PKHD1L1, TRPS1, and EXT1 for hair length, and DDHD1, BMP4, SEMA3C, and FOXP1 for the DI. These findings suggest that significant QTL, combined with functional candidate genes, can be leveraged to improve the genetic quality of the Sapsaree population. This study provides a foundation for more effective breeding strategies aimed at preserving and enhancing the unique traits of this Korean dog breed.

Animals↗

PubMed2026

Integrated Genome-Wide Association Studies and Selection Signature Analysis Reveal the Genetic Architecture of the Wattle Trait in Goats.

Wattles are finger-like appendages on the ventral neck of goats, serving as a distinctive morphological marker for breed identification that serves potential implications for production performance. However, their genetic basis remains incompletely characterized. Here, we integrated a genome-wide association study (GWAS) and selection signature analysis to identify candidate genes and genomic regions associated with the wattle trait in goats. Using a linear mixed model, GWAS on 463 goats (23 wattled and 440 non-wattled) identified 385 quantitative trait loci (QTLs) at a 5% false discovery rate, yielding 346 candidate genes. The most significant association signal was observed on chromosome 10 (72.61-73.48 Mb), where the lead SNP (rs636481767) is located within a region containing GJD2, GREM1, and FMN1, showing strong linkage disequilibrium (r2 > 0.6) with surrounding loci. Subsequent selection signature analysis (23 wattled and 23 non-wattled) identified 83 genomic regions harboring 119 candidate genes. The strongest signals were detected at MFSD14B on chromosome 8 (FST = 0.154, log2π-ratio = 2.611) and PDLIM7 on chromosome 7 (FST = 0.144, log2π-ratio = 0.806). KEGG pathway enrichment analysis revealed that GWAS-associated genes were involved in glycosylation and immune responses, whereas selection-signature genes were enriched in DNA repair and the Hippo, Notch, and Wnt pathways. Furthermore, cross-species PheWAS revealed that human FMN1 is associated with dermatological, skeletal, and metabolic phenotypes, while porcine FMN1 is associated with backfat thickness and loin muscle depth. Overall, this study provides molecular markers of potential value for goat breeding and pinpoints key candidate genes for future functional validation of wattle development.

Animals↗

PubMed2026

Genome-wide association studies of plant traits and functional analysis of leaf development-related genes in citrus.

Labor-saving and high-light-efficiency tree architecture is a key breeding objective for woody fruit trees like citrus. However, population genetics information on these traits remains limited. In this study, tree architecture, thorn, and leaf traits were evaluated in 353 F2 progeny derived from a cross between Clementine mandarin and precocious trifoliate orange-an early-flowering variety. A random subset of 300 offspring was sequenced for a genome-wide association study (GWAS), which detected 10 216 significantly associated SNPs and defined several major quantitative trait loci (QTLs) for the target traits. Subsequent bulked segregant analysis (BSA) and GWAS on individuals with extreme compound leaf phenotypes mapped the causal gene(s) to a 0.8 Mb region (22.15-22.95 Mb) on chromosome 4. Genetic analysis across multiple hybrid combinations confirmed that the compound leaf trait in trifoliate orange is dominantly inherited and follows Mendelian segregation. Transcriptome profiling of parental leaves at different developmental stages identified a KNOX gene, CiKNAT6, as a candidate. Further validation using CAPS markers and Hi-Tom sequencing demonstrated tight linkage between an InDel polymorphism in CiKNAT6 and leaf shape across diverse citrus species and the F2 population, with co-segregation observed for the compound leaf trait. Due to alternative splicing producing seven splice variants, the CiKNAT6 DNA sequence was selected for genetic transformation experiments. Functional analysis revealed that the Clementine mandarin allele of CiKNAT6 is non-functional owing to an InDel, whereas ectopic expression of the trifoliate orange allele in tobacco and lemon induced leaf curling and reduced leaf size. CRISPR-Cas9 knockout of CiKNAT6 in trifoliate orange resulted in increased leaf area. These findings provide valuable genetic resources and insights for future studies on tree architecture and leaf morphology.

Plant Leaves↗

PubMed2026

A multi-model genome-wide association study identifies genetic variants underlying resistance to Largemouth Bass Ranavirus (LMBV) in Micropterus salmoides.

Largemouth bass (Micropterus salmoides) is an economically important freshwater aquaculture species, yet recurrent outbreaks of Largemouth Bass Ranavirus (LMBV) continue to impair production and cause substantial losses. The genetic basis of host variation in LMBV resistance remains insufficiently characterized. Here, we applied a multi-model genome-wide association study (GWAS) to identify loci associated with resistance following a controlled challenge with the LMBV-23PY strain. Whole-genome resequencing was performed for 146 phenotyped fish, including 72 susceptible and 74 resistant individuals. After stringent quality control, 877,262 high-quality variants were retained and tested using six GWAS models. Across binary survival status and survival time phenotypes, 32 shared suggestive variants were consistently detected across models, representing suggestive loci for LMBV-23PY resistance. Genes within ±50 kb of these loci were annotated, and functional enrichment highlighted immune- and redox-related biological processes. Three prioritized candidates-GSTT3L (glutathione S-transferase theta-3-like), CGRP2 (calcitonin gene-related peptide 2), and NPPC (natriuretic peptide C)-were associated with pathways involved in oxidative stress responses and immune regulation. Collectively, these results provide insight into the genetic architecture of LMBV-23PY resistance in largemouth bass and identify suggestive variants and associated candidate genes for downstream validation, functional interrogation, and the development of marker-assisted and genome-enabled breeding strategies.

Animals↗

PubMed2025

Genome-wide association study of long COVID.

Infections can lead to persistent symptoms and diseases such as shingles after varicella zoster or rheumatic fever after streptococcal infections. Similarly, severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection can result in long coronavirus disease (COVID), typically manifesting as fatigue, pulmonary symptoms and cognitive dysfunction. The biological mechanisms behind long COVID remain unclear. We performed a genome-wide association study for long COVID including up to 6,450 long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. We discovered an association of FOXP4 with long COVID, independent of its previously identified association with severe COVID-19. The signal was replicated in 9,500 long COVID cases and 798,835 population controls. Given the transcription factor FOXP4's role in lung physiology and pathology, our findings highlight the importance of lung function in the pathophysiology of long COVID.

Humans↗

PubMed2025

Adaptive laboratory evolution of Micrococcus luteus and identification of genes associated with radioresistance through genome-wide association study.

Micrococcus luteus (V017) is a Gram-positive bacterium that was isolated from a sterilization area exposed to 60Co radiation. In this study, we performed an adaptive laboratory evolution experiment with M. luteus, exposing it to 24 continuous cycles of gamma irradiation at four different doses (1.5 kGy, 3.5 kGy, 5.5 kGy, and 7.5 kGy). This led to the creation of four evolved populations with different levels of radioresistance, which were positively correlated with the radiation dose applied. The survival rate of the evolved population that underwent adaptive treatment at the highest dose (7.5 kGy) was 0.69% after exposure to 5.5 kGy, which is about five orders of magnitude higher than that of the original strain V017. Furthermore, 76 evolved strains were selected from these populations, and their genomes were re-sequenced, uncovering a total of 3072 mutations. A genome-wide association study identified 56 single nucleotide polymorphisms (SNPs) significantly associated with radioresistance, linked to 62 candidate genes. Ultimately, 9 genes were selected for functional validation. Inactivating 6 of these genes, including H0H31_RS03855 (SMC family ATPase, SbcC), H0H31_RS04250 (ribonuclease HII), H0H31_RS04570 (endonuclease VIII), H0H31_RS07595 (bifunctional 3'-5' exonuclease/DNA polymerase I), H0H31_RS00170 (serine/threonine phosphatase PPP), and H0H31_RS05860 (CBS-domain-containing protein), significantly increased sensitivity to gamma radiation, underscoring their importance in radioresistance.

Micrococcus luteus↗