Background:Hepatocellular carcinoma(HCC)is one of the most common cancers worldwide and is prevalent in East Asia.Although genome-wide association studies(GWASs)of HCC have identified 23 risk regions,the susceptibilit...Background:Hepatocellular carcinoma(HCC)is one of the most common cancers worldwide and is prevalent in East Asia.Although genome-wide association studies(GWASs)of HCC have identified 23 risk regions,the susceptibility genes underlying these associa-tions largely remain unclear.To identify novel candidate genes for HCC,we conducted liver single-tissue and cross-tissue transcrip-tomewide association studies(TWASs)in two populations of East Asia.Methods:GWAS summary statistics of 2,514 subjects(1,161 HCC cases and 1,353 controls)from the Chinese Qidong cohort and 161,323 subjects(2,122 HCC cases and 159,201 controls)from the BioBank Japan project were used to conduct TWAS analysis.The single-tissue and cross-tissue TWAS approaches were both used to detect the association between susceptible genes and the risk of HCC.TWAS identified genes were further annotated by Metascape,UALCAN,GEPIA2,and DepMap.Results:We identified 22 novel genes at 16 independent loci significantly associated with HCC risk after Bonferroni correction.Of these,13 genes were located in novel regions.Besides,we found 83 genes overlapped in the Chinese and Japanese cohorts with P<0.05,of which,three genes(NUAK2,HLA-DQA1,and ATP6V1G2)were discerned by both single-tissue and cross-tissue TWAS approaches.Among the genes identified through TWAS,a significant proportion of them exhibit a credible role in HCC biology,such as FAM96B,HSPA5,POLRMT,MPHOSPH10,and RABL2A.HLA-DQA1,NUAK2,and HSPA5 associated with the process of carcinogenesis in HCC as previously reported.Conclusions:Our findings highlight the value of leveraging the gene expression data to identify new candidate genes beyond the GWAS associations and could further provide a genetic insight for the biology of HCC.展开更多
Southern corn rust(SCR)is an airborne fungal disease caused by Puccinia polysora Underw.(P.polysora)that adversely impacts maize quality and yields worldwide.Screening for new elite SCR-resistant maize loci or genes h...Southern corn rust(SCR)is an airborne fungal disease caused by Puccinia polysora Underw.(P.polysora)that adversely impacts maize quality and yields worldwide.Screening for new elite SCR-resistant maize loci or genes has the potential to enhance overall resistance to this pathogen.Using phenotypic SCR resistance-related data collected over two years and three geographical environments,a genome-wide association study was carried out in this work,which eventually identified 91 loci that were substantially correlated with SCR susceptibility.These included 13 loci that were significant in at least three environments and overlapped with 74 candidate genes(B73_RefGen_v4).Comparative transcriptomic analyses were then performed to identify the genes related to SCR infection,with 2,586 and 797 differentially expressed genes(DEGs)ultimately being identified in the resistant Qi319and susceptible 8112 inbred lines following P.polysora infection,respectively,including 306 genes common to both lines.Subsequent integrative multi-omics investigations identified four potential candidate SCR response-related genes.One of these genes is ZmHCT9,which encodes the protein hydroxycinnamoyl transferase 9.This gene was up-regulated in susceptible inbred lines and linked to greater P.polysora resistance as confirmed through cucumber mosaic virus(CMV)-based virus induced-gene silencing(VIGS)system-mediated gene silencing.These data provide important insights into the genetic basis of the maize SCR response.They will be useful for for future research on potential genes related to SCR resistance in maize.展开更多
Alkaline soil is characterized by high soluble salt content,elevated pH levels,and ionic imbalance,all of which collectively intensify the harmful effects of alkaline stress on plants.To gain molecular insights into a...Alkaline soil is characterized by high soluble salt content,elevated pH levels,and ionic imbalance,all of which collectively intensify the harmful effects of alkaline stress on plants.To gain molecular insights into alkaline tolerance(AT),we evaluated 13 AT-related traits in 508 diverse rice accessions from the 3K Rice Germplasm Project at the seedling stage.A total of 2929764,2059114,and 1365868 single nucleotide polymorphisms were used to identify alkaline-tolerance QTLs via genome-wide association studies(GWAS)in the entire population as well as in the xian and geng subpopulations,respectively.Candidate genes and their superior haplotypes were further identified through gene-based association,haplotype analysis,and gene function annotation.In total,99 QTLs were identified for AT by GWAS,and three genes(LOC_Os03g49050 for qSSD3.1,LOC_Os05g48760 for qSKC5,and LOC_Os12g01922 for qSNC12)were selected as the most promising candidate genes.Furthermore,we successfully mined superior alleles of key candidate genes from natural variants associated with AT-related traits.This study identified crucial candidate genes and their favorable alleles for AT traits,laying a foundation for further gene cloning and the development of AT rice varieties via marker-assisted selection.展开更多
Resilience traits in pig populations allow animals to deal better with infectious disease and suboptimal production environments.The data on daily weight,feed intake and feed behaviors in pigs are collected in test pe...Resilience traits in pig populations allow animals to deal better with infectious disease and suboptimal production environments.The data on daily weight,feed intake and feed behaviors in pigs are collected in test period by automated feeding stations,which facilitate to evaluate the resilience traits.In this study,we adopted the root mean square error(RMSE)of ordinary least squares(OLS)and the negative residuals of quantile regression(QR)to generate four different novel resilience traits using daily records of feed intake and feed duration between 90 and 180 days of age in a population of commercial Duroc pigs.The genome-wide association studies(GWAS)based on single-and two-trait mixed models were carried out on 550 pigs using 48,603 single nucleotide polymorphisms(SNPs)to identify genomic regions associated with resilience traits in growing pigs.We further focused on the GWAS signals to conduct gene annotation,colocalization with multi-tissue eQTL summary statistics of PigGTEx project and identification of enhancers and promoters using the publicly available data.The genomic heritabilities of four novel resilience traits ranged from 0.09 to 0.41.The pairwise genetic and phenotypic correlations ranged from 0.16 to 0.95 and from 0.05 to 0.36,respectively.Twenty-seven SNPs were identified to be significantly associated with these resilience traits.They were distributed on nine chromosomes(SSC1,SSC2,SSC6,SSC7,SSC8,SSC12,SSC14,SSC16 and SSC17).After annotation,39 QTLs and 49 candidate genes were identified.Several of these are functionally relevant candidate genes including OTUD4,TIFA and CARD14,which are involved in the host immune response,disease susceptibility and signal transduction.Eight unique SNPs were found to be causal in both GWAS and eQTL analyses across 15 tissues.Notably,one SNP(rs80794541)was associated with eQTLs identified concurrently across seven tissues/cell types,including the macrophage cell type.Furthermore,four significant SNPs(rs81467127,rs81356029,rs80794541 and rs81305085)were linked to the function of the primed enhancer,active element,and poised promoter in five pig tissues.Using the porcine fibroblast HiC dataset,SNP(rs81356029)on SSC2 regulates the CARNS1 and SSH3,while SNP(rs80794541)on SSC7 regulates the H2AC6.In this study,we generated four novel resilience traits and identified SNPs significantly associated with these resilience traits in a Duroc pig population.GWAS signals were associated with candidate genes involving in the immune traits,and were linked to the crucial regulatory elements as well.Our findings will contribute to elucidating the genetic mechanism that can enhance genome-enabled breeding and inform further research on resilience in domestic pigs.展开更多
Seedlessness has always been a valuable quality characteristic of edible grape varieties.Although the production of seedless grapes has been ongoing for decades,the genetic complexity of seedless grapes is not yet ful...Seedlessness has always been a valuable quality characteristic of edible grape varieties.Although the production of seedless grapes has been ongoing for decades,the genetic complexity of seedless grapes is not yet fully understood.Therefore,determining the genetic mechanisms and key regulatory genes of seedless grapes is of great significance for seedless grape breeding and meeting market demands.The emergence of high-throughput analysis software offers greater possibilities for mining genes related to plant organ development.Specifically,to mine a greater number of candidate genes related to grape seed traits,this study used the seed trait parameters analyzed by Tomato Analyzer as the target trait and then used a genome-wide association study(GWAS)to mine candidate genes.In the two-year analysis using principal component analysis(PCA),we extracted five principal components with a cumulative contribution rate of 96.586%.The cumulative contribution rate for component 1 reached 87.352%.Correlation analysis revealed correlation coefficients ranging from 0.54 to 0.98 among the seven basic traits.The GWAS results indicated that 370 SNP loci were significantly correlated with seed traits.These SNP loci were distributed on 18 chromosomes,except for chromosome 4,with most SNP loci distributed on chromosome 18.Based on the physical location of single nucleotide polymorphism(SNP)markers significantly associated with seed-related traits in the grape reference genome,candidate genes are screened within the range of linkage disequilibrium(LD)attenuation distance,both upstream and downstream of the significant SNP loci.These candidate genes were mainly transcription factor-related genes(VvMADS4 and VvMADS5),ubiquitin ligase-related genes(E3 ubiquitin ligase BIG BROTHER),serine/threonine protein kinase-related genes,and carbohydrate metabolism-related genes(Sucrose Synthase 2)and simultaneously controlled multiple(at least two or more)seed traits.These results indicate that seed traits are jointly regulated by some genes involved in seed morphology regulation.In this work,we identified new gene loci related to grape seed traits.Identifying molecular markers closely related to these seed traits is of great significance for breeding seedless grape varieties.展开更多
Background:Rice grain morphology—including traits such as awn length,hull color,size,and shape—is of central importance to yield,quality,and domestication,yet comprehensive quantification at scale has remained chall...Background:Rice grain morphology—including traits such as awn length,hull color,size,and shape—is of central importance to yield,quality,and domestication,yet comprehensive quantification at scale has remained challenging.Apromising solution has been provided by the integration of high-throughput imaging with genomic analysis.Methods:A standardized 2D image-processing pipeline was established to extract four categories of traits—awn length,hull color,projected grain area,and shape descriptors via PCA of normalized contours—from high-resolution photographs of 229 Oryza sativa japonica landraces.Genome-wide association analyses were then performed using a mixed linearmodel to control for population structure and kinship.Results:Broad phenotypic diversity was evident in awn length,hull coloration,grain dimensions,and morphological shape,with the first principal component explaining the dominant axis of shape variation.Known awn regulators GAD1/OsRAE2(chr 8;P=4.75×10^(-17))and An-1(chr 4;P=1.91×10^(-6))were identified.The hull color gene Rd(chr 1;P=3.13×10^(-6))was detected.A novel locus on chr 12 at 8.75 Mb with Os12g0257600(P=1.41×10^(-8)),and the known grain size gene FLO2(chr 4;P=8.28×10^(-6))were associated with projected area.Shape PC1 was mapped to GLW7/OsSPL13(chr 7;P=3.86×10^(-10)),NAL2/OsWOX3A(chr 11;P=1.41×10^(-11)),and OsGIF1(chr 11;P=1.27×10^(-8)).Conclusions:This study demonstrates that image-based phenotyping combined with genome-wide association studies(GWAS)can efficiently reveal both established and novel genetic determinants of rice grain morphology.These findings provide actionable targets for marker-assisted selection and genome editing to tailor grain traits in rice breeding programs.展开更多
Rice grain yield is primarily determined by three key agronomic traits:panicle number,grain number per panicle,and grain weight(GW).However,the inherent tradeoffs among these yield components remain a persistent chall...Rice grain yield is primarily determined by three key agronomic traits:panicle number,grain number per panicle,and grain weight(GW).However,the inherent tradeoffs among these yield components remain a persistent challenge in rice breeding programs.Notably,compared with GW,brown rice weight(BRW)provides a more direct metric associated with actual grain yield potential.In this study,we conducted a two-year replicated genome-wide association study to elucidate the genetic architecture of BRW and identify new loci regulating GW.Among seven consistently detected loci across experimental replicates,four were not co-localized with previously reported genes associated with BRW or GW traits.BRW1.1,one of the four newly identified loci,was found to encode a novel RNA-binding protein.Functional characterization revealed that BRW1.1 acts as a negative regulator of BRW,potentially through modulating mRNA translation processes.Intriguingly,through integrated analysis of mutant phenotypes and haplotype variations,we demonstrated that BRW1.1 mediates the physiological tradeoff between GW and panicle number.This study not only delineates the genetic determinants of BRW but also identifies BRW1.1 as a promising molecular target for breaking the yield component tradeoff in precision rice breeding.展开更多
The genetic mechanism determining amylose content(AC)and its impact on eating and cooking quality(ECQ)of rice is highly complex.To elucidate the genetic basis of AC in rice,the Ting’s core collection was used to iden...The genetic mechanism determining amylose content(AC)and its impact on eating and cooking quality(ECQ)of rice is highly complex.To elucidate the genetic basis of AC in rice,the Ting’s core collection was used to identify novel AC genes/loci through genome-wide association analysis(GWAS)using more than 5.0 million single nucleotide polymorphisms(SNPs).In this study,12 genes related to AC,including the major gene Wx and 11 minor genes,were detected using the EMMAX method.A novel gene,LR,encoding a nucleotide-binding leucine-rich-repeat(LRR)receptor(NLR)family protein,was selected for functional study.When LR was knocked out using CRISPR/Cas9,the AC decreased significantly.Furthermore,the AC in varieties was significantly higher with Haplotype A compared to Haplotypes B and C of LR.Notably,two natural variations,SNP-385(Thr-Hap.A vs Ala-Haps.B and C)and SNP-758(Ser-Hap.A vs Asn-Haps.B and C),in the coding region of LR might play critical roles in regulating AC and serve as potential targets for cultivating rice with diverse amylose contents.展开更多
The width of rice leaves determines the size of the photosynthetic area.Optimizing rice leaf width can improve the photosynthetic rate,thereby increasing rice yield.In this study,a genome-wide association study(GWAS)w...The width of rice leaves determines the size of the photosynthetic area.Optimizing rice leaf width can improve the photosynthetic rate,thereby increasing rice yield.In this study,a genome-wide association study(GWAS)was conducted by 225 rice germplasm resources to explore the genetic basis of rice flag leaf width(FLW).We identified nine QTLs associated with FLW(qFLWs),with phenotypic contribution rates ranging from 3.17%to 14.37%.Near-isogenic lines(NILs)were developed for fine-mapping of qFLW11,and the function of FLW11 was further verified.We narrowed down q FLW11 to an 87-kb interval,which contains five genes.展开更多
AIM:To investigate the association of macrophage migration inhibitory factor(MIF)promoter polymorphisms with inflammatory bowel disease(IBD)risk.METHODS:One thousand and six New Zealand Caucasian cases and 540 Caucasi...AIM:To investigate the association of macrophage migration inhibitory factor(MIF)promoter polymorphisms with inflammatory bowel disease(IBD)risk.METHODS:One thousand and six New Zealand Caucasian cases and 540 Caucasian controls were genotyped for the MIF SNP-173G>C(rs755622)and the repeat polymorphism CATT5-8(rs5844572)using a predesigned TaqMan SNP assay and capillary electrophoresis,respectively.Data were analysed for single site and haplotype association with IBD risk and phenotype.Meta-analysis was employed,to assess cumulative evidence of association of MIF-173G>C with IBD.All published genotype data for MIF-173G>C in IBD were identified using PubMed and subsequently searching the references of all PubMed-identified studies.Imputed genotypes for MIF-173G>C were generated from the Wellcome Trust Case Control Consortium(and National Institute of Diabetes and Digestive and Kidney Diseases).Separate meta-analyses were performed on Caucasian Crohn’s disease(CD)(3863 patients,6031controls),Caucasian ulcerative colitis(UC)(1260 patients,1987 controls),and East Asian UC(416 patients and 789 controls)datasets using the Mantel-Haenszel method.The New Zealand dataset had 93%power,and the meta-analyses had 100%power to detect an effect size of OR=1.40 atα=0.05,respectively.RESULTS:In our New Zealand dataset,single-site analysis found no evidence of association of MIF polymorphisms with overall risk of CD,UC,and IBD or disease phenotype(all P values>0.05).Haplotype analysis found the CATT5/-173C haplotype occurred at a higher frequency in New Zealand controls compared to IBD patients(0.6 vs 0.01;P=0.03,OR=0.22;95%CI:0.05-0.99),but this association did not survive bonferroni correction.Meta-analysis of our New Zealand MIF-173G>C data with data from seven additional Caucasian datasets using a random effects model found no association of MIF polymorphisms with CD,UC,or overall IBD.Similarly,meta-analysis of all published MIF-173G>C data from East Asian datasets(416UC patients,789 controls)found no association of this promoter polymorphism with UC.展开更多
Objective: In the past few decades, more than 500 reports have been published on the relationship between single nucleotide polymorphisms(SNPs) on candidate genes and gastric cancer(GC) risk. Previous findings have be...Objective: In the past few decades, more than 500 reports have been published on the relationship between single nucleotide polymorphisms(SNPs) on candidate genes and gastric cancer(GC) risk. Previous findings have been disputed and are controversial. Therefore, we performed this article to summarize and assess the credibility and strength of genetic polymorphisms on the risk of GC.Methods: We used Web of Science, PubMed, and Medline to identify meta-analyses published before July 30 th, 2018 that assessed associations between variants on candidate genes and the risk of GC. Cumulative epidemiological evidence of statistical associations was assessed combining Venice criteria and a false-positive report probability(FPRP) test.Results: Sixty-one variants demonstrated a significant association with GC risk, whereas 29 demonstrated no association. Nine variants on nine genes were rated as presenting strong cumulative epidemiological evidence for a nominally significant association with GC risk, including APE1(rs1760944), DNMT1(rs16999593), ERCC5(rs751402), GSTT1(null/presence), MDM2(rs2278744), PPARG(rs1801282), TLR4(rs4986790), IL-17 F(rs763780), and CASP8(rs3834129). Eleven SNPs were rated as moderate, and 33 SNPs were rated as weak. We also used the FPRP test to identify 13 noteworthy SNPs in five genome-wide association studies.Conclusions: Sixty-one variants are significantly associated with GC risk, and 29 variants are not associated with GC risk;however, five variants on five genes presented strong evidence for an association upgraded from moderate. Further study of these variants may be needed in the future. Our study also provides referenced information for the genetic predisposition to GC.展开更多
Esophageal cancer(EC) caused about 395000 deaths in 2010. China has the most cases of EC and EC is the fourth leading cause of cancer death in China. Esophageal squamous cell carcinoma(ESCC) is the predominant histolo...Esophageal cancer(EC) caused about 395000 deaths in 2010. China has the most cases of EC and EC is the fourth leading cause of cancer death in China. Esophageal squamous cell carcinoma(ESCC) is the predominant histologic type(90%-95%), while the incidence of esophageal adenocarcinoma(EAC) remains extremely low in China. Traditional epidemiological studies have revealed that environmental carcinogens are risk factors for EC. Molecular epidemiological studies revealed that susceptibility to EC is influenced by both environmental and genetic risk factors. Of all the risk factors for EC, some are associated with the risk of ESCC and others with the risk of EAC. However, the details and mechanisms of risk factors involved in the process for EC are unclear. The advanced methods and techniques used in human genome studies bring a great opportunity for researchers to explore and identify the details of those risk factors or susceptibility genes involved inthe process of EC. Human genome epidemiology is a new branch of epidemiology, which leads the epidemiology study from the molecular epidemiology era to the era of genome wide association studies(GWAS). Here we review the epidemiological studies of EC(especially ESCC) in the era of GWAS, and provide an overview of the general risk factors and those genomic variants(genes, SNPs, miRNAs, proteins) involved in the process of ESCC.展开更多
The clinical outcome of hepatitis B virus(HBV) infection depends on the success or failure of the immune responses to HBV,and varies widely among individuals,ranging from asymptomatic self-limited infection,inactive c...The clinical outcome of hepatitis B virus(HBV) infection depends on the success or failure of the immune responses to HBV,and varies widely among individuals,ranging from asymptomatic self-limited infection,inactive carrier state,chronic hepatitis,cirrhosis,hepatocellular carcinoma,to liver failure,depending on the success or failure of immune response to HBV.Genome-wide association studies(GWAS) identified key genetic factors influencing the pathogenesis of HBV-related traits.In this review,we discuss GWAS for persistence of HBV infection,antibody response to hepatitis B vaccine,and HBV-related advanced liver diseases.HBV persistence is associated with multiple genes with diverse roles in immune mechanisms.The strongest associations are found within the classical human leukocyte antigen(HLA) genes,highlighting the central role of antigen presentation in the immune response to HBV.Associated variants affect both epitope binding specificities and expression levels of HLA molecules.Several other susceptibility genes regulate the magnitude of adaptive immune responses,determining immunity vs tolerance.HBV persistence and nonresponse to vaccine share the same risk variants,implying overlapping genetic bases.On the other hand,the risk variants for HBV-related advanced liver diseases are largely different,suggesting different host-virus dynamics in acute vs chronic HBV infections.The findings of these GWAS are likely to pave the way for developing more effective preventive and therapeutic interventions by personalizing the management of HBV infection.展开更多
Genome-wide association studies(GWAS)have identified several genetic variants associated with coronary heart disease(CHD),and variations in plasma lipoproteins and blood pressure(BP).Loci corresponding to CDKN2A/CDKN2...Genome-wide association studies(GWAS)have identified several genetic variants associated with coronary heart disease(CHD),and variations in plasma lipoproteins and blood pressure(BP).Loci corresponding to CDKN2A/CDKN2B/ANRIL,MTHFD1L,CELSR2,PSRC1 and SORT1 genes have been associated with CHD,and TMEM57,DOCK7,CELSR2,APOB,ABCG5,HMGCR,TRIB1,FADS2/S3,LDLR,NCAN and TOMM40-APOE with total cholesterol.Similarly,CELSR2-PSRC1-SORT1,PCSK9,APOB,HMGCR,NCAN-CILP2-PBX4,LDLR,TOMM40-APOE,and APOC1-APOE are associated with variations in low-density lipoprotein cholesterol levels.Altogether,forty,forty three and twenty loci have been associated with high-density lipoprotein cholesterol,triglycerides and BP phenotypes,respectively.Some of these identified loci are common for all the traits,some do not map to functional genes,and some are located in genes that encode for proteins not previously known to be involved in the biological pathway of the trait.GWAS have been successful at identifying new and unexpected genetic loci common to diseases and traits,thus rapidly providing key novel insights into disease biology.Since genotype information is fixed,with minimum biological variability,it is useful in early life risk prediction.However,these variants explain only a small proportion of the observed variance of these traits.Therefore,the utility of genetic determinants in assessing risk at later stages of life has limited immediate clinical impact.The future application of genetic screening will be in identifying risk groups early in life to direct targeted preventive measures.展开更多
Sheath blight(SB) caused by the soil borne pathogen Rhizoctonia solani is one of the most serious global rice diseases. Breeding resistant cultivar is the most economical and effective strategy to control the disease....Sheath blight(SB) caused by the soil borne pathogen Rhizoctonia solani is one of the most serious global rice diseases. Breeding resistant cultivar is the most economical and effective strategy to control the disease. However, no rice varieties are completely resistant to SB, and only a few reliable quantitative trait loci(QTLs) linked with SB resistance have been identified to date. In this study, we conducted a genome-wide association study(GWAS) of SB resistance using 299 varieties from the rice diversity panel 1(RDP1) that were genotyped using 44 000 high-density single nucleotide polymorphism(SNP) markers. Through artificial inoculation, we found that only 36.5% of the tested varieties displayed resistance or moderate resistance to SB. In particular, the aromatic and aus sub-populations displayed higher SB resistance than the tropical japonica(TRJ), indica and temperate japonica sub-populations. Seven varieties showed similar resistance levels to the resistant control YSBR1. GWAS identified at least 11 SNP loci significantly associated with SB resistance in the three independent trials, leading to the identification of two reliable QTLs, qSB-3 and qSB-6, on chromosomes 3 and 6. Using favorable alleles or haplotypes of significantly associated SNP loci, we estimated that both QTLs had obvious effects on reducing SB disease severity and can be used for enhancing SB resistance, especially in improving SB resistance of TRJ sub-population rice varieties. These results provided important information and genetic materials for developing SB resistant varieties through breeding.展开更多
Porcine carcass traits and organ weights have important economic roles in the swine industry. A total of 576 animals from a Large White×Minzhu intercross population were genotyped using the Illumina PorcineSNP60K...Porcine carcass traits and organ weights have important economic roles in the swine industry. A total of 576 animals from a Large White×Minzhu intercross population were genotyped using the Illumina PorcineSNP60K Beadchip and were phenotyped for 10 traits, speciifcally, backfat thickness （6-7 libs）, carcass length, carcass weight, foot weight, head weight, heart weight, leaf fat weight, liver weight, lung weight and slaughter body weight. The genome-wide association study （GWAS） was assessed by Genome Wide Rapid Association using the mixed model and regression-genomic control approach. A total of 31 single nucleotide polymorphisms （SNPs） （with the most signiifcant SNP being MARC0033464, P value=6.80×10-13） were located in a 9.76-Mb （31.24-41.00 Mb） region on SSC7 and were found to be signiifcantly associated with one or more carcass traits and organ weights. High percentage of phenotypic variance explanation was observed for each trait ranging from 31.21 to 67.42%. Linkage analysis revealed one haplotype block of 495 kb, in which the most signiifcant SNP being MARC0033464 was contained, on SSC7 at complete linkage disequilibrium. Annotation of the pig reference genome suggested 6 genes （GRM4, HMGA1, NUDT3, RPS10, SPDEF and PACSIN1） in this candidate linkage disequilibrium （LD） interval. Functional analysis indicated that the HMGA1 gene presents the prime biological candidate for carcass traits and organ weights in pig, with potential application in breeding programs.展开更多
Genome-wide association studies(GWAS) of myopia and refractive error have generated exciting results and identified novel risk-associated loci. However, the interpretation of the findings of GWAS of complex diseases i...Genome-wide association studies(GWAS) of myopia and refractive error have generated exciting results and identified novel risk-associated loci. However, the interpretation of the findings of GWAS of complex diseases is not straightforward and has remained challenging. This review provides a brief summary of the main focus on the advantages and limitations of GWAS of myopia, with potential strategies that may contribute to further insight into the genetics of myopia in the post-GWAS or omics era.展开更多
Vitamin E,consisting of tocopherols and tocotrienols,serves as a lipid-soluble antioxidant in sweet corn kernels,providing nutrients to both plants and humans.Though the key genes involved in the vitamin E biosynthesi...Vitamin E,consisting of tocopherols and tocotrienols,serves as a lipid-soluble antioxidant in sweet corn kernels,providing nutrients to both plants and humans.Though the key genes involved in the vitamin E biosynthesis pathway have been identified in plants,the genetic architecture of vitamin E content in sweet corn kernels remains largely unclear.In the present study,an association panel of 204 inbred lines of sweet corn was constructed.Seven compounds of vitamin E were quantified in sweet corn kernels at 28 days after pollination.A total of 119 loci for vitamin E were identified using a genome-wide association study based on genotyping by sequencing,and a genetic network of vitamin E was constructed.Candidate genes identified were involved mainly in RNA regulation and protein metabolism.The known gene ZmVTE4,encodingγ-tocopherol methyltransferase,was significantly associated with four traits(α-tocopherol,α-tocotrienol,theα/γ-tocopherol ratio,and theα/γ-tocotrienol ratio).The effects of two causative markers on ZmVTE4 were validated by haplotype analysis.Finally,two elite cultivars(Yuetian 9 and Yuetian 22)with a 4.5-fold increase in the sum ofα-andγ-tocopherols were developed by marker-assisted selection,demonstrating the successful biofortification of sweet corn.Three genes(DAHPS,ADT2,and cmu2)involved in chorismate and tyrosine synthesis were significantly associated with theα/γ-tocotrienol ratio.These results shed light on the genetic architecture of vitamin E and may accelerate the nutritional improvement of sweet corn.展开更多
Fusarium ear rot(FER)is a destructive maize fungal disease worldwide.In this study,three tropical maize populations consisting of 874 inbred lines were used to perform genomewide association study(GWAS)and genomic pre...Fusarium ear rot(FER)is a destructive maize fungal disease worldwide.In this study,three tropical maize populations consisting of 874 inbred lines were used to perform genomewide association study(GWAS)and genomic prediction(GP)analyses of FER resistance.Broad phenotypic variation and high heritability for FER were observed,although it was highly influenced by large genotype-by-environment interactions.In the 874 inbred lines,GWAS with general linear model(GLM)identified 3034 single-nucleotide polymorphisms(SNPs)significantly associated with FER resistance at the P-value threshold of 1×10^(-5),the average phenotypic variation explained(PVE)by these associations was 3%with a range from 2.33%to 6.92%,and 49 of these associations had PVE values greater than 5%.The GWAS analysis with mixed linear model(MLM)identified 19 significantly associated SNPs at the P-value threshold of 1×10^(-4),the average PVE of these associations was 1.60%with a range from 1.39%to 2.04%.Within each of the three populations,the number of significantly associated SNPs identified by GLM and MLM ranged from 25 to 41,and from 5 to 22,respectively.Overlapping SNP associations across populations were rare.A few stable genomic regions conferring FER resistance were identified,which located in bins 3.04/05,7.02/04,9.00/01,9.04,9.06/07,and 10.03/04.The genomic regions in bins 9.00/01 and 9.04 are new.GP produced moderate accuracies with genome-wide markers,and relatively high accuracies with SNP associations detected from GWAS.Moderate prediction accuracies were observed when the training and validation sets were closely related.These results implied that FER resistance in maize is controlled by minor QTL with small effects,and highly influenced by the genetic background of the populations studied.Genomic selection(GS)by incorporating SNP associations detected from GWAS is a promising tool for improving FER resistance in maize.展开更多
The human face is a heritable surface with many complex sensory organs.In recent years,many genetic loci associated with facial features have been reported in different populations,yet there is a lack of studies on th...The human face is a heritable surface with many complex sensory organs.In recent years,many genetic loci associated with facial features have been reported in different populations,yet there is a lack of studies on the Han Chinese population.Here,we report a genome-wide association study of 3D normal human faces of 2,659 Han Chinese with autosegment phenotypes of facial morphology.We identify singlenucleotide polymorphisms(SNPs)encompassing four genomic regions showing significant associations with different facial regions,including SNPs in DENND1 B associated with the chin,SNPs among PISRT1 associated with eyes,SNPs between DCHS2 and SFRP2 associated with the nose,and SNPs in VPS13 B associated with the nose.We replicate 24 SNPs from previously reported genetic loci in different populations,whose candidate genes are DCHS2,SUPT3 H,HOXD1,SOX9,PAX3,and EDAR.These results provide a more comprehensive understanding of the genetic basis of variation in human facial morphology.展开更多
基金supported by the National Natural Science Foundation of China[grant number:82272312]the 100 Top Talent Programs of Sun Yat-sen University[grant number:58000-12230029]the Shenzhen-Hong Kong-Macao Science and Technology Project(Category C project)[grant number:SGDX20220530111403024].
文摘Background:Hepatocellular carcinoma(HCC)is one of the most common cancers worldwide and is prevalent in East Asia.Although genome-wide association studies(GWASs)of HCC have identified 23 risk regions,the susceptibility genes underlying these associa-tions largely remain unclear.To identify novel candidate genes for HCC,we conducted liver single-tissue and cross-tissue transcrip-tomewide association studies(TWASs)in two populations of East Asia.Methods:GWAS summary statistics of 2,514 subjects(1,161 HCC cases and 1,353 controls)from the Chinese Qidong cohort and 161,323 subjects(2,122 HCC cases and 159,201 controls)from the BioBank Japan project were used to conduct TWAS analysis.The single-tissue and cross-tissue TWAS approaches were both used to detect the association between susceptible genes and the risk of HCC.TWAS identified genes were further annotated by Metascape,UALCAN,GEPIA2,and DepMap.Results:We identified 22 novel genes at 16 independent loci significantly associated with HCC risk after Bonferroni correction.Of these,13 genes were located in novel regions.Besides,we found 83 genes overlapped in the Chinese and Japanese cohorts with P<0.05,of which,three genes(NUAK2,HLA-DQA1,and ATP6V1G2)were discerned by both single-tissue and cross-tissue TWAS approaches.Among the genes identified through TWAS,a significant proportion of them exhibit a credible role in HCC biology,such as FAM96B,HSPA5,POLRMT,MPHOSPH10,and RABL2A.HLA-DQA1,NUAK2,and HSPA5 associated with the process of carcinogenesis in HCC as previously reported.Conclusions:Our findings highlight the value of leveraging the gene expression data to identify new candidate genes beyond the GWAS associations and could further provide a genetic insight for the biology of HCC.
基金supported by the National Key R&D Program of China(2022YFD1201802)the Shandong Key R&D Program,China(2022CXGC010607)+2 种基金the Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences(CAAS-ZDRW202109)the Agricultural Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences(CAAS-ASTIP2017-ICS)the Subproject of the Major Project of Science and Technology in Shanxi Province,China(202201140601025-1-02)。
文摘Southern corn rust(SCR)is an airborne fungal disease caused by Puccinia polysora Underw.(P.polysora)that adversely impacts maize quality and yields worldwide.Screening for new elite SCR-resistant maize loci or genes has the potential to enhance overall resistance to this pathogen.Using phenotypic SCR resistance-related data collected over two years and three geographical environments,a genome-wide association study was carried out in this work,which eventually identified 91 loci that were substantially correlated with SCR susceptibility.These included 13 loci that were significant in at least three environments and overlapped with 74 candidate genes(B73_RefGen_v4).Comparative transcriptomic analyses were then performed to identify the genes related to SCR infection,with 2,586 and 797 differentially expressed genes(DEGs)ultimately being identified in the resistant Qi319and susceptible 8112 inbred lines following P.polysora infection,respectively,including 306 genes common to both lines.Subsequent integrative multi-omics investigations identified four potential candidate SCR response-related genes.One of these genes is ZmHCT9,which encodes the protein hydroxycinnamoyl transferase 9.This gene was up-regulated in susceptible inbred lines and linked to greater P.polysora resistance as confirmed through cucumber mosaic virus(CMV)-based virus induced-gene silencing(VIGS)system-mediated gene silencing.These data provide important insights into the genetic basis of the maize SCR response.They will be useful for for future research on potential genes related to SCR resistance in maize.
基金supported by the Shenzhen Science and Technology Program,China(Grant No.KCXFZ20211020163808012)the Nanfan Special Project,Chinese Academy of Agricultural Sciences,China(Grant No.YBXM2426).
文摘Alkaline soil is characterized by high soluble salt content,elevated pH levels,and ionic imbalance,all of which collectively intensify the harmful effects of alkaline stress on plants.To gain molecular insights into alkaline tolerance(AT),we evaluated 13 AT-related traits in 508 diverse rice accessions from the 3K Rice Germplasm Project at the seedling stage.A total of 2929764,2059114,and 1365868 single nucleotide polymorphisms were used to identify alkaline-tolerance QTLs via genome-wide association studies(GWAS)in the entire population as well as in the xian and geng subpopulations,respectively.Candidate genes and their superior haplotypes were further identified through gene-based association,haplotype analysis,and gene function annotation.In total,99 QTLs were identified for AT by GWAS,and three genes(LOC_Os03g49050 for qSSD3.1,LOC_Os05g48760 for qSKC5,and LOC_Os12g01922 for qSNC12)were selected as the most promising candidate genes.Furthermore,we successfully mined superior alleles of key candidate genes from natural variants associated with AT-related traits.This study identified crucial candidate genes and their favorable alleles for AT traits,laying a foundation for further gene cloning and the development of AT rice varieties via marker-assisted selection.
基金funded by the National Key Research and Development Program of China(2024YFF1000100 and 2021YFD1301102)the National Natural Science Foundations of China(32172702)the National Agricultural Science and Technology Innovation Program,Chinese Academy of Agricultural Sciences(ASTIP-IAS02).
文摘Resilience traits in pig populations allow animals to deal better with infectious disease and suboptimal production environments.The data on daily weight,feed intake and feed behaviors in pigs are collected in test period by automated feeding stations,which facilitate to evaluate the resilience traits.In this study,we adopted the root mean square error(RMSE)of ordinary least squares(OLS)and the negative residuals of quantile regression(QR)to generate four different novel resilience traits using daily records of feed intake and feed duration between 90 and 180 days of age in a population of commercial Duroc pigs.The genome-wide association studies(GWAS)based on single-and two-trait mixed models were carried out on 550 pigs using 48,603 single nucleotide polymorphisms(SNPs)to identify genomic regions associated with resilience traits in growing pigs.We further focused on the GWAS signals to conduct gene annotation,colocalization with multi-tissue eQTL summary statistics of PigGTEx project and identification of enhancers and promoters using the publicly available data.The genomic heritabilities of four novel resilience traits ranged from 0.09 to 0.41.The pairwise genetic and phenotypic correlations ranged from 0.16 to 0.95 and from 0.05 to 0.36,respectively.Twenty-seven SNPs were identified to be significantly associated with these resilience traits.They were distributed on nine chromosomes(SSC1,SSC2,SSC6,SSC7,SSC8,SSC12,SSC14,SSC16 and SSC17).After annotation,39 QTLs and 49 candidate genes were identified.Several of these are functionally relevant candidate genes including OTUD4,TIFA and CARD14,which are involved in the host immune response,disease susceptibility and signal transduction.Eight unique SNPs were found to be causal in both GWAS and eQTL analyses across 15 tissues.Notably,one SNP(rs80794541)was associated with eQTLs identified concurrently across seven tissues/cell types,including the macrophage cell type.Furthermore,four significant SNPs(rs81467127,rs81356029,rs80794541 and rs81305085)were linked to the function of the primed enhancer,active element,and poised promoter in five pig tissues.Using the porcine fibroblast HiC dataset,SNP(rs81356029)on SSC2 regulates the CARNS1 and SSH3,while SNP(rs80794541)on SSC7 regulates the H2AC6.In this study,we generated four novel resilience traits and identified SNPs significantly associated with these resilience traits in a Duroc pig population.GWAS signals were associated with candidate genes involving in the immune traits,and were linked to the crucial regulatory elements as well.Our findings will contribute to elucidating the genetic mechanism that can enhance genome-enabled breeding and inform further research on resilience in domestic pigs.
基金supported by grants from the Basic Research Business Fees for Public Welfare in Xinjiang Autonomous Region(Mining candidate genes related to grape seed traits based on GWAS,KY2023028)the Xinjiang Uygur Autonomous Region Tianchi Talent-Young Doctor for Chuan Zhang(Revealing the domestication history of Xinjiang native grape varieties and genetic analysis of important agronomic traits)the Xinjiang Academy of Agricultural Sciences Youth Science and Technology Backbone Innovation Ability Training Project(xjnkq-2023006).
文摘Seedlessness has always been a valuable quality characteristic of edible grape varieties.Although the production of seedless grapes has been ongoing for decades,the genetic complexity of seedless grapes is not yet fully understood.Therefore,determining the genetic mechanisms and key regulatory genes of seedless grapes is of great significance for seedless grape breeding and meeting market demands.The emergence of high-throughput analysis software offers greater possibilities for mining genes related to plant organ development.Specifically,to mine a greater number of candidate genes related to grape seed traits,this study used the seed trait parameters analyzed by Tomato Analyzer as the target trait and then used a genome-wide association study(GWAS)to mine candidate genes.In the two-year analysis using principal component analysis(PCA),we extracted five principal components with a cumulative contribution rate of 96.586%.The cumulative contribution rate for component 1 reached 87.352%.Correlation analysis revealed correlation coefficients ranging from 0.54 to 0.98 among the seven basic traits.The GWAS results indicated that 370 SNP loci were significantly correlated with seed traits.These SNP loci were distributed on 18 chromosomes,except for chromosome 4,with most SNP loci distributed on chromosome 18.Based on the physical location of single nucleotide polymorphism(SNP)markers significantly associated with seed-related traits in the grape reference genome,candidate genes are screened within the range of linkage disequilibrium(LD)attenuation distance,both upstream and downstream of the significant SNP loci.These candidate genes were mainly transcription factor-related genes(VvMADS4 and VvMADS5),ubiquitin ligase-related genes(E3 ubiquitin ligase BIG BROTHER),serine/threonine protein kinase-related genes,and carbohydrate metabolism-related genes(Sucrose Synthase 2)and simultaneously controlled multiple(at least two or more)seed traits.These results indicate that seed traits are jointly regulated by some genes involved in seed morphology regulation.In this work,we identified new gene loci related to grape seed traits.Identifying molecular markers closely related to these seed traits is of great significance for breeding seedless grape varieties.
文摘Background:Rice grain morphology—including traits such as awn length,hull color,size,and shape—is of central importance to yield,quality,and domestication,yet comprehensive quantification at scale has remained challenging.Apromising solution has been provided by the integration of high-throughput imaging with genomic analysis.Methods:A standardized 2D image-processing pipeline was established to extract four categories of traits—awn length,hull color,projected grain area,and shape descriptors via PCA of normalized contours—from high-resolution photographs of 229 Oryza sativa japonica landraces.Genome-wide association analyses were then performed using a mixed linearmodel to control for population structure and kinship.Results:Broad phenotypic diversity was evident in awn length,hull coloration,grain dimensions,and morphological shape,with the first principal component explaining the dominant axis of shape variation.Known awn regulators GAD1/OsRAE2(chr 8;P=4.75×10^(-17))and An-1(chr 4;P=1.91×10^(-6))were identified.The hull color gene Rd(chr 1;P=3.13×10^(-6))was detected.A novel locus on chr 12 at 8.75 Mb with Os12g0257600(P=1.41×10^(-8)),and the known grain size gene FLO2(chr 4;P=8.28×10^(-6))were associated with projected area.Shape PC1 was mapped to GLW7/OsSPL13(chr 7;P=3.86×10^(-10)),NAL2/OsWOX3A(chr 11;P=1.41×10^(-11)),and OsGIF1(chr 11;P=1.27×10^(-8)).Conclusions:This study demonstrates that image-based phenotyping combined with genome-wide association studies(GWAS)can efficiently reveal both established and novel genetic determinants of rice grain morphology.These findings provide actionable targets for marker-assisted selection and genome editing to tailor grain traits in rice breeding programs.
基金supported by the National Natural Science Foundation of China(Grant Nos.32000377,32172037,and 32472211)the Biological Breeding-National Science and Technology Major Project,China(Grant No.2023ZD04068)+2 种基金the Fundamental Research Funds for the Central Universities,China(Grant No.KJQN202103)the open funds of the State Key Laboratory of Crop Genetics&Germplasm Enhancement and Utilization,China(Grant No.ZW202401)the Cyrus Tang Innovation Center for Crop Seed Industry,China.
文摘Rice grain yield is primarily determined by three key agronomic traits:panicle number,grain number per panicle,and grain weight(GW).However,the inherent tradeoffs among these yield components remain a persistent challenge in rice breeding programs.Notably,compared with GW,brown rice weight(BRW)provides a more direct metric associated with actual grain yield potential.In this study,we conducted a two-year replicated genome-wide association study to elucidate the genetic architecture of BRW and identify new loci regulating GW.Among seven consistently detected loci across experimental replicates,four were not co-localized with previously reported genes associated with BRW or GW traits.BRW1.1,one of the four newly identified loci,was found to encode a novel RNA-binding protein.Functional characterization revealed that BRW1.1 acts as a negative regulator of BRW,potentially through modulating mRNA translation processes.Intriguingly,through integrated analysis of mutant phenotypes and haplotype variations,we demonstrated that BRW1.1 mediates the physiological tradeoff between GW and panicle number.This study not only delineates the genetic determinants of BRW but also identifies BRW1.1 as a promising molecular target for breaking the yield component tradeoff in precision rice breeding.
基金supported by the Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Technology City,China(Grant No.2021JJLH0041)the Zhejiang Provincial Natural Science Foundation,China(Grant No.LY23C130006)+3 种基金the National Natural Science Foundation of China(Grant No.32472207)Nanfan Special Project,Chinese Academy of Agricultural Sciences(Grant Nos.YBXM2436 and YBXM2326)the Hainan Province Science and Technology Special Fund,China(Grant No.ZDYF2022XDNY256)the Innovational Fund for Scientific and Technological Personnel of Hainan Province,China(Grant No.KJRC2023B24).
文摘The genetic mechanism determining amylose content(AC)and its impact on eating and cooking quality(ECQ)of rice is highly complex.To elucidate the genetic basis of AC in rice,the Ting’s core collection was used to identify novel AC genes/loci through genome-wide association analysis(GWAS)using more than 5.0 million single nucleotide polymorphisms(SNPs).In this study,12 genes related to AC,including the major gene Wx and 11 minor genes,were detected using the EMMAX method.A novel gene,LR,encoding a nucleotide-binding leucine-rich-repeat(LRR)receptor(NLR)family protein,was selected for functional study.When LR was knocked out using CRISPR/Cas9,the AC decreased significantly.Furthermore,the AC in varieties was significantly higher with Haplotype A compared to Haplotypes B and C of LR.Notably,two natural variations,SNP-385(Thr-Hap.A vs Ala-Haps.B and C)and SNP-758(Ser-Hap.A vs Asn-Haps.B and C),in the coding region of LR might play critical roles in regulating AC and serve as potential targets for cultivating rice with diverse amylose contents.
基金supported by the Zhejiang Provincial Natural Science Foundation,China(Grant No.LD24C130001)the National Natural Science Foundation of China(Grant Nos.W2412006 and 32372125)+3 种基金the Hainan Provincial Natural Science Foundation,China(Grant Nos.GHYF2025029 and YBXM2422)the Innovation Platform for Academicians of Hainan Province,China(Grant No.YSPTZX202502)the National Modern Agricultural Industry Technology System Project,China(Grant No.CARS-01-18)the Special Support Program of Chinese Academy of Agricultural Sciences(Grant Nos.NKYCLJ-C-2021-015 and CAAS-ZDRW202401)。
文摘The width of rice leaves determines the size of the photosynthetic area.Optimizing rice leaf width can improve the photosynthetic rate,thereby increasing rice yield.In this study,a genome-wide association study(GWAS)was conducted by 225 rice germplasm resources to explore the genetic basis of rice flag leaf width(FLW).We identified nine QTLs associated with FLW(qFLWs),with phenotypic contribution rates ranging from 3.17%to 14.37%.Near-isogenic lines(NILs)were developed for fine-mapping of qFLW11,and the function of FLW11 was further verified.We narrowed down q FLW11 to an 87-kb interval,which contains five genes.
基金Supported by The Health Research Council of New ZealandScholarships from the Canterbury Gastroenterology Research Trust,New Zealand Society of Gastroenterology Ferring Scholarship,the Bowel and Liver Trust Canterbury and from the University of Otago to Falvey JD
文摘AIM:To investigate the association of macrophage migration inhibitory factor(MIF)promoter polymorphisms with inflammatory bowel disease(IBD)risk.METHODS:One thousand and six New Zealand Caucasian cases and 540 Caucasian controls were genotyped for the MIF SNP-173G>C(rs755622)and the repeat polymorphism CATT5-8(rs5844572)using a predesigned TaqMan SNP assay and capillary electrophoresis,respectively.Data were analysed for single site and haplotype association with IBD risk and phenotype.Meta-analysis was employed,to assess cumulative evidence of association of MIF-173G>C with IBD.All published genotype data for MIF-173G>C in IBD were identified using PubMed and subsequently searching the references of all PubMed-identified studies.Imputed genotypes for MIF-173G>C were generated from the Wellcome Trust Case Control Consortium(and National Institute of Diabetes and Digestive and Kidney Diseases).Separate meta-analyses were performed on Caucasian Crohn’s disease(CD)(3863 patients,6031controls),Caucasian ulcerative colitis(UC)(1260 patients,1987 controls),and East Asian UC(416 patients and 789 controls)datasets using the Mantel-Haenszel method.The New Zealand dataset had 93%power,and the meta-analyses had 100%power to detect an effect size of OR=1.40 atα=0.05,respectively.RESULTS:In our New Zealand dataset,single-site analysis found no evidence of association of MIF polymorphisms with overall risk of CD,UC,and IBD or disease phenotype(all P values>0.05).Haplotype analysis found the CATT5/-173C haplotype occurred at a higher frequency in New Zealand controls compared to IBD patients(0.6 vs 0.01;P=0.03,OR=0.22;95%CI:0.05-0.99),but this association did not survive bonferroni correction.Meta-analysis of our New Zealand MIF-173G>C data with data from seven additional Caucasian datasets using a random effects model found no association of MIF polymorphisms with CD,UC,or overall IBD.Similarly,meta-analysis of all published MIF-173G>C data from East Asian datasets(416UC patients,789 controls)found no association of this promoter polymorphism with UC.
文摘Objective: In the past few decades, more than 500 reports have been published on the relationship between single nucleotide polymorphisms(SNPs) on candidate genes and gastric cancer(GC) risk. Previous findings have been disputed and are controversial. Therefore, we performed this article to summarize and assess the credibility and strength of genetic polymorphisms on the risk of GC.Methods: We used Web of Science, PubMed, and Medline to identify meta-analyses published before July 30 th, 2018 that assessed associations between variants on candidate genes and the risk of GC. Cumulative epidemiological evidence of statistical associations was assessed combining Venice criteria and a false-positive report probability(FPRP) test.Results: Sixty-one variants demonstrated a significant association with GC risk, whereas 29 demonstrated no association. Nine variants on nine genes were rated as presenting strong cumulative epidemiological evidence for a nominally significant association with GC risk, including APE1(rs1760944), DNMT1(rs16999593), ERCC5(rs751402), GSTT1(null/presence), MDM2(rs2278744), PPARG(rs1801282), TLR4(rs4986790), IL-17 F(rs763780), and CASP8(rs3834129). Eleven SNPs were rated as moderate, and 33 SNPs were rated as weak. We also used the FPRP test to identify 13 noteworthy SNPs in five genome-wide association studies.Conclusions: Sixty-one variants are significantly associated with GC risk, and 29 variants are not associated with GC risk;however, five variants on five genes presented strong evidence for an association upgraded from moderate. Further study of these variants may be needed in the future. Our study also provides referenced information for the genetic predisposition to GC.
文摘Esophageal cancer(EC) caused about 395000 deaths in 2010. China has the most cases of EC and EC is the fourth leading cause of cancer death in China. Esophageal squamous cell carcinoma(ESCC) is the predominant histologic type(90%-95%), while the incidence of esophageal adenocarcinoma(EAC) remains extremely low in China. Traditional epidemiological studies have revealed that environmental carcinogens are risk factors for EC. Molecular epidemiological studies revealed that susceptibility to EC is influenced by both environmental and genetic risk factors. Of all the risk factors for EC, some are associated with the risk of ESCC and others with the risk of EAC. However, the details and mechanisms of risk factors involved in the process for EC are unclear. The advanced methods and techniques used in human genome studies bring a great opportunity for researchers to explore and identify the details of those risk factors or susceptibility genes involved inthe process of EC. Human genome epidemiology is a new branch of epidemiology, which leads the epidemiology study from the molecular epidemiology era to the era of genome wide association studies(GWAS). Here we review the epidemiological studies of EC(especially ESCC) in the era of GWAS, and provide an overview of the general risk factors and those genomic variants(genes, SNPs, miRNAs, proteins) involved in the process of ESCC.
文摘The clinical outcome of hepatitis B virus(HBV) infection depends on the success or failure of the immune responses to HBV,and varies widely among individuals,ranging from asymptomatic self-limited infection,inactive carrier state,chronic hepatitis,cirrhosis,hepatocellular carcinoma,to liver failure,depending on the success or failure of immune response to HBV.Genome-wide association studies(GWAS) identified key genetic factors influencing the pathogenesis of HBV-related traits.In this review,we discuss GWAS for persistence of HBV infection,antibody response to hepatitis B vaccine,and HBV-related advanced liver diseases.HBV persistence is associated with multiple genes with diverse roles in immune mechanisms.The strongest associations are found within the classical human leukocyte antigen(HLA) genes,highlighting the central role of antigen presentation in the immune response to HBV.Associated variants affect both epitope binding specificities and expression levels of HLA molecules.Several other susceptibility genes regulate the magnitude of adaptive immune responses,determining immunity vs tolerance.HBV persistence and nonresponse to vaccine share the same risk variants,implying overlapping genetic bases.On the other hand,the risk variants for HBV-related advanced liver diseases are largely different,suggesting different host-virus dynamics in acute vs chronic HBV infections.The findings of these GWAS are likely to pave the way for developing more effective preventive and therapeutic interventions by personalizing the management of HBV infection.
基金Supported by A Wellcome Trust Capacity Strengthening Strategic Award to the Public Health Foundation of India and a consortium of UK universities(to Jeemon P)Research grants from National Heart Lung and Blood Institute,United States of America (HHSN286200900026C)National Institute of Health,United States of America(1D43HD065249)(to Prabhakaran D)
文摘Genome-wide association studies(GWAS)have identified several genetic variants associated with coronary heart disease(CHD),and variations in plasma lipoproteins and blood pressure(BP).Loci corresponding to CDKN2A/CDKN2B/ANRIL,MTHFD1L,CELSR2,PSRC1 and SORT1 genes have been associated with CHD,and TMEM57,DOCK7,CELSR2,APOB,ABCG5,HMGCR,TRIB1,FADS2/S3,LDLR,NCAN and TOMM40-APOE with total cholesterol.Similarly,CELSR2-PSRC1-SORT1,PCSK9,APOB,HMGCR,NCAN-CILP2-PBX4,LDLR,TOMM40-APOE,and APOC1-APOE are associated with variations in low-density lipoprotein cholesterol levels.Altogether,forty,forty three and twenty loci have been associated with high-density lipoprotein cholesterol,triglycerides and BP phenotypes,respectively.Some of these identified loci are common for all the traits,some do not map to functional genes,and some are located in genes that encode for proteins not previously known to be involved in the biological pathway of the trait.GWAS have been successful at identifying new and unexpected genetic loci common to diseases and traits,thus rapidly providing key novel insights into disease biology.Since genotype information is fixed,with minimum biological variability,it is useful in early life risk prediction.However,these variants explain only a small proportion of the observed variance of these traits.Therefore,the utility of genetic determinants in assessing risk at later stages of life has limited immediate clinical impact.The future application of genetic screening will be in identifying risk groups early in life to direct targeted preventive measures.
基金partially supported by the Open Funding from State Key Laboratory for Biology of Plant Diseases and Insect Pests(Grant No.SKLOF201403)by the Natural Science Foundation of China(Grant Nos.31571748 and 31701057)the Natural Science Foundation of Jiangsu Province,China(Grant Nos.BK20171293 and BK20141291)
文摘Sheath blight(SB) caused by the soil borne pathogen Rhizoctonia solani is one of the most serious global rice diseases. Breeding resistant cultivar is the most economical and effective strategy to control the disease. However, no rice varieties are completely resistant to SB, and only a few reliable quantitative trait loci(QTLs) linked with SB resistance have been identified to date. In this study, we conducted a genome-wide association study(GWAS) of SB resistance using 299 varieties from the rice diversity panel 1(RDP1) that were genotyped using 44 000 high-density single nucleotide polymorphism(SNP) markers. Through artificial inoculation, we found that only 36.5% of the tested varieties displayed resistance or moderate resistance to SB. In particular, the aromatic and aus sub-populations displayed higher SB resistance than the tropical japonica(TRJ), indica and temperate japonica sub-populations. Seven varieties showed similar resistance levels to the resistant control YSBR1. GWAS identified at least 11 SNP loci significantly associated with SB resistance in the three independent trials, leading to the identification of two reliable QTLs, qSB-3 and qSB-6, on chromosomes 3 and 6. Using favorable alleles or haplotypes of significantly associated SNP loci, we estimated that both QTLs had obvious effects on reducing SB disease severity and can be used for enhancing SB resistance, especially in improving SB resistance of TRJ sub-population rice varieties. These results provided important information and genetic materials for developing SB resistant varieties through breeding.
基金supported by the Agricultural Science and Technology Innovation Program, China (ASTIPIAS02)the National Key Technology R&D Program of China (2011BAD28B01)+2 种基金the National Natural Science Foundation of China (31201781)the Earmarked Fund for Modern Agroindustry Technology Research System, National Technology Program of China (2011ZX08006-003)the Chinese Academy of Agricultural Sciences Foundation (2011cj-5, 2012ZL069 and 2014ywf-yb-8)
文摘Porcine carcass traits and organ weights have important economic roles in the swine industry. A total of 576 animals from a Large White×Minzhu intercross population were genotyped using the Illumina PorcineSNP60K Beadchip and were phenotyped for 10 traits, speciifcally, backfat thickness （6-7 libs）, carcass length, carcass weight, foot weight, head weight, heart weight, leaf fat weight, liver weight, lung weight and slaughter body weight. The genome-wide association study （GWAS） was assessed by Genome Wide Rapid Association using the mixed model and regression-genomic control approach. A total of 31 single nucleotide polymorphisms （SNPs） （with the most signiifcant SNP being MARC0033464, P value=6.80×10-13） were located in a 9.76-Mb （31.24-41.00 Mb） region on SSC7 and were found to be signiifcantly associated with one or more carcass traits and organ weights. High percentage of phenotypic variance explanation was observed for each trait ranging from 31.21 to 67.42%. Linkage analysis revealed one haplotype block of 495 kb, in which the most signiifcant SNP being MARC0033464 was contained, on SSC7 at complete linkage disequilibrium. Annotation of the pig reference genome suggested 6 genes （GRM4, HMGA1, NUDT3, RPS10, SPDEF and PACSIN1） in this candidate linkage disequilibrium （LD） interval. Functional analysis indicated that the HMGA1 gene presents the prime biological candidate for carcass traits and organ weights in pig, with potential application in breeding programs.
基金Supported by Projects of Science&Technology Department of Sichuan Province(No.2019YJ0381)
文摘Genome-wide association studies(GWAS) of myopia and refractive error have generated exciting results and identified novel risk-associated loci. However, the interpretation of the findings of GWAS of complex diseases is not straightforward and has remained challenging. This review provides a brief summary of the main focus on the advantages and limitations of GWAS of myopia, with potential strategies that may contribute to further insight into the genetics of myopia in the post-GWAS or omics era.
基金the National Natural Science Foundation of China(31601309)Science and Technology Planning Project of Guangdong Province(2016B020233004,2015A020209063,2017B090907023)+2 种基金Science and Technology Planning Project of Guangzhou(201804020081)Agricultural Development and Rural Work Special Project-Modern Seed Industry Enhancement Project of Guangdong(201788)the Excellent PhD Program of Guangdong Academy of Agricultural Sciences(2017).
文摘Vitamin E,consisting of tocopherols and tocotrienols,serves as a lipid-soluble antioxidant in sweet corn kernels,providing nutrients to both plants and humans.Though the key genes involved in the vitamin E biosynthesis pathway have been identified in plants,the genetic architecture of vitamin E content in sweet corn kernels remains largely unclear.In the present study,an association panel of 204 inbred lines of sweet corn was constructed.Seven compounds of vitamin E were quantified in sweet corn kernels at 28 days after pollination.A total of 119 loci for vitamin E were identified using a genome-wide association study based on genotyping by sequencing,and a genetic network of vitamin E was constructed.Candidate genes identified were involved mainly in RNA regulation and protein metabolism.The known gene ZmVTE4,encodingγ-tocopherol methyltransferase,was significantly associated with four traits(α-tocopherol,α-tocotrienol,theα/γ-tocopherol ratio,and theα/γ-tocotrienol ratio).The effects of two causative markers on ZmVTE4 were validated by haplotype analysis.Finally,two elite cultivars(Yuetian 9 and Yuetian 22)with a 4.5-fold increase in the sum ofα-andγ-tocopherols were developed by marker-assisted selection,demonstrating the successful biofortification of sweet corn.Three genes(DAHPS,ADT2,and cmu2)involved in chorismate and tyrosine synthesis were significantly associated with theα/γ-tocotrienol ratio.These results shed light on the genetic architecture of vitamin E and may accelerate the nutritional improvement of sweet corn.
基金The authors gratefully acknowledge the financial support from the MasAgro project funded by Mexico’s Secretary of Agriculture and Rural Development(SADER),the Genomic Open-source Breeding Informatics Initiative(GOBII)(grant number OPP1093167)supported by the Bill&Melinda Gates Foundation,and the CGIAR Research Program(CRP)on maize(MAIZE)MAIZE receives W1&W2 support from the Governments of Australia,Belgium,Canada,China,France,India,Japan,the Republic of Korea,Mexico,Netherlands,New Zealand,Norway,Sweden,Switzerland,the United Kingdom,USA,and the World Bank+2 种基金The authors also thank the National Natural Science Foundation of China(grant number 31801442)the CIMMYT–China Specialty Maize Research Center Project funded by the Shanghai Municipal Finance Bureauthe China Scholarship Council.
文摘Fusarium ear rot(FER)is a destructive maize fungal disease worldwide.In this study,three tropical maize populations consisting of 874 inbred lines were used to perform genomewide association study(GWAS)and genomic prediction(GP)analyses of FER resistance.Broad phenotypic variation and high heritability for FER were observed,although it was highly influenced by large genotype-by-environment interactions.In the 874 inbred lines,GWAS with general linear model(GLM)identified 3034 single-nucleotide polymorphisms(SNPs)significantly associated with FER resistance at the P-value threshold of 1×10^(-5),the average phenotypic variation explained(PVE)by these associations was 3%with a range from 2.33%to 6.92%,and 49 of these associations had PVE values greater than 5%.The GWAS analysis with mixed linear model(MLM)identified 19 significantly associated SNPs at the P-value threshold of 1×10^(-4),the average PVE of these associations was 1.60%with a range from 1.39%to 2.04%.Within each of the three populations,the number of significantly associated SNPs identified by GLM and MLM ranged from 25 to 41,and from 5 to 22,respectively.Overlapping SNP associations across populations were rare.A few stable genomic regions conferring FER resistance were identified,which located in bins 3.04/05,7.02/04,9.00/01,9.04,9.06/07,and 10.03/04.The genomic regions in bins 9.00/01 and 9.04 are new.GP produced moderate accuracies with genome-wide markers,and relatively high accuracies with SNP associations detected from GWAS.Moderate prediction accuracies were observed when the training and validation sets were closely related.These results implied that FER resistance in maize is controlled by minor QTL with small effects,and highly influenced by the genetic background of the populations studied.Genomic selection(GS)by incorporating SNP associations detected from GWAS is a promising tool for improving FER resistance in maize.
基金funded by the Max-Planck-Gesellschaft Partner Group Grant(K.T.)the National Natural Science Foundation of China(31371267,31322030,and 91331108,K.T.+10 种基金91631307,S.W.30890034,31271338,L.J.and 31525014,91731303,31771388,31961130380,and 32041008,S.X.)supported by the National Basic Research Program(2015FY111700,L.J.)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01,L.J.,S.X.,and S.W.)the Ministry of Education(311016,L.J.)Strategic Priority Research Program of the Chinese Academy of Sciences(CAS)(XDB13040000,S.X.and S.W.)the UK Royal Society-Newton Advanced Fellowship(NAFn R1n191094)Key Research Program of Frontier Sciences(QYZDJ-SSW-SYS009)of the Chinese Academy of Sciencesthe support of a National Thousand Young Talents Award and a Max Planck-CAS Paul Gerson Unna Independent Research Group Leadership Award(S.W.)the Science and Technology Commission of Shanghai Municipality(16JC1400504,S.W.)。
文摘The human face is a heritable surface with many complex sensory organs.In recent years,many genetic loci associated with facial features have been reported in different populations,yet there is a lack of studies on the Han Chinese population.Here,we report a genome-wide association study of 3D normal human faces of 2,659 Han Chinese with autosegment phenotypes of facial morphology.We identify singlenucleotide polymorphisms(SNPs)encompassing four genomic regions showing significant associations with different facial regions,including SNPs in DENND1 B associated with the chin,SNPs among PISRT1 associated with eyes,SNPs between DCHS2 and SFRP2 associated with the nose,and SNPs in VPS13 B associated with the nose.We replicate 24 SNPs from previously reported genetic loci in different populations,whose candidate genes are DCHS2,SUPT3 H,HOXD1,SOX9,PAX3,and EDAR.These results provide a more comprehensive understanding of the genetic basis of variation in human facial morphology.
