Phosphorus(P)is essential for living plants,and P deficiency is one of the key factors limiting the yield in rapeseed production worldwide.As the most important organ for plants,root morphology traits(RMTs)play a key ...Phosphorus(P)is essential for living plants,and P deficiency is one of the key factors limiting the yield in rapeseed production worldwide.As the most important organ for plants,root morphology traits(RMTs)play a key role in P absorption.To investigate the genetic variability of RMT under low P availability,we dissected the genetic structure of RMTs by genome-wide association studies(GWAS),linkage mapping and candidate gene association studies(CGAS).A total of 52 suggestive loci were associated with RMTs under P stress conditions in 405 oilseed rape accessions.The purple acid phosphatase gene BnPAP17 was found to control the lateral root number(LRN)and root dry weight(RDW)under low P stress.The expression of BnPAP17 was increased in shoot tissue in P-efficient cultivars compared to root tissue and P-inefficient cultivars in response to low P stress.Moreover,the haplotype of BnPAP17^(Hap3)was detected for the selective breeding of P efficiency in oilseed rape.Over-expression of the BnPAP17^(Hap3)could promote the shoot and root growth with enhanced tolerance to low P stress and organic phosphorus(Po)utilization in oilseed rape.Collectively,these findings increase our understanding of the mechanisms underlying BnPAP17-mediated low P stress tolerance in oilseed rape.展开更多
Nitrogen(N)fertilizer application is essential for crop-plant growth and development.Identifying genetic loci associated with N-use efficiency(NUE)could increase wheat yields and reduce environmental pollution caused ...Nitrogen(N)fertilizer application is essential for crop-plant growth and development.Identifying genetic loci associated with N-use efficiency(NUE)could increase wheat yields and reduce environmental pollution caused by overfertilization.We subjected a panel of 389 wheat accessions to N and chlorate(a nitrate analog)treatments to identify quantitative trait loci(QTL)controlling NUE-associated traits at the wheat seedling stage.Genotyping the panel with a 660K single-nucleotide polymorphism(SNP)array,we identified 397 SNPs associated with N-sensitivity index and chlorate inhibition rate.These SNPs were merged into 49 QTL,of which eight were multi-environment stable QTL and 27 were located near previously reported QTL.A set of 135 candidate genes near the 49 QTL included TaBOX(F-box family protein)and TaERF(ethylene-responsive transcription factor).A Tabox mutant was more sensitive to low-N stress than the wild-type plant.We developed two functional markers for Hap 1,the favorable allele of TaBOX.展开更多
Rice cooking and eating qualities(CEQ)are mainly determined by cooked rice textural parameters and starch physicochemical properties.However,the genetic bases of grain texture and starch properties in rice have not be...Rice cooking and eating qualities(CEQ)are mainly determined by cooked rice textural parameters and starch physicochemical properties.However,the genetic bases of grain texture and starch properties in rice have not been fully understood.We conducted a genome-wide association study for apparent amylose content(AAC),starch pasting viscosities,and cooked rice textural parameters using 279 indica rice accessions from the 3000 Rice Genome Project.We identified 26 QTLs in the whole population and detected single nucleotide polymorphisms(SNPs)with the lowest P-value at the Waxy(Wx)locus for all traits except pasting temperature and cohesiveness.Additionally,we detected significant SNPs at the SUBSTANDARD STARCH GRAIN6(SSG6)locus for AAC,setback(SB),hardness,adhesiveness,chewiness(CHEW),gumminess(GUM),and resilience.We subsequently divided the population using a SNP adjacent to the Waxy locus,and identified 23 QTLs and 12 QTLs in two sub-panels,WxT and WxA,respectively.In these sub-panels,SSG6 was also identified to be associated with pasting parameters,including peak viscosity,hot paste viscosity,cold paste viscosity,and consistency viscosity.Furthermore,a candidate gene encoding monosaccharide transporter 5(OsMST5)was identified to be associated with AAC,breakdown,SB,CHEW,and GUM.In total,39 QTLs were co-localized with known genes or previously reported QTLs.These identified genes and QTLs provide valuable information for genetic manipulation to improve rice CEQ.展开更多
Upland cotton(Gossypium hirsutum)is the most important plant producing natural fibers for the textile industry.In this study,we first investigated the phenotypic variation of seven agronomic traits of 273 diverse cott...Upland cotton(Gossypium hirsutum)is the most important plant producing natural fibers for the textile industry.In this study,we first investigated the phenotypic variation of seven agronomic traits of 273 diverse cotton accessions in the years 2017 and 2018,which were from 18 geographical regions.We found large variations among the traits in different geographical regions and only half of the traits in either years 2017 or 2018 followed a normal distribution.We then genotyped the collection with 81,612 high quality SNPs.Phylogenetic tree and population structure revealed a diverse genetic structure of the core collection,and geographical diversification was an important factor,but account for part of the variances of genetic diversification.We then performed genome-wide association study for the seven traits in the years 2017 and 2018,and the average values of each trait in the two years,respectively.We identified a total of 19 significant marker-trait associations and found that Pollen Ole e 1 allergen/extension could be the candidate gene associated with the fall-off cotton bolls from the last three branches.In addition,large variations were observed for the heritability of traits in the years 2017 and 2018.These results provide new potential candidate genes for further functional validation,which could be useful for genetic improvement and breeding of new cotton cultivars with better agronomic performances.展开更多
BACKGROUND John Henryism(JH)is a strategy for dealing with chronic psychological stress characterized by high levels of physical effort and work.Cynicism is a belief that people are motivated primarily by self-interes...BACKGROUND John Henryism(JH)is a strategy for dealing with chronic psychological stress characterized by high levels of physical effort and work.Cynicism is a belief that people are motivated primarily by self-interest.High scores on the JH scale and cynicism measures correlate with an increased risk of cardiovascular disease.High cynicism is also a hallmark of burnout syndrome,another known risk factor for heart disease.AIM To evaluate possible interactions between JH and cynicism hoping to clarify risk factors of burnout.METHODS We analyzed genetic and psychological data available from the Database of Genotypes and Phenotypes for genome-wide associations with these traits.We split the total available samples and used plink to perform the association studies on the discovery set(n=1852,80%)and tested for replication using the validation set(n=465).We used scikit-learn to perform supervised machine learning for developing genetic risk algorithms.RESULTS We identified 2,727,and 204 genetic associations for scores on the JH,cynicism and cynical distrust(CD)scales,respectively.We also found 173 associations with high cynicism,109 with high CD,but no associations with high JH.We also produced polygenic classifiers for high cynicism using machine learning with areas under the receiver operator characteristics curve greater than 0.7.CONCLUSION We found significant genetic components to these traits but no evidence of an interaction.Therefore,while there may be a genetic risk,JH is not likely a burnout risk factor.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
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
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
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
Appearance and cooked rice elongation are key quality traits of rice. Although some QTL for these traits have been identified, understanding of the genetic relationship between them remains limited. In the present stu...Appearance and cooked rice elongation are key quality traits of rice. Although some QTL for these traits have been identified, understanding of the genetic relationship between them remains limited. In the present study, large phenotypic variation was observed in 760 accessions from the 3 K Rice Genomes Project for both appearance quality and cooked rice elongation. Most component traits of appearance quality and cooked rice elongation showed significant pairwise correlations, but a low correlation was found between appearance quality and cooked rice elongation. A genome-wide association study identified 74 QTL distributed on all 12 chromosomes for grain length, grain width, length to width ratio, degree of endosperm with chalkiness, rice elongation difference, and elongation index. Thirteen regions containing QTL stably expressed in multiple environments and/or exerting pleiotropic effects on multiple traits were detected. By gene-based association analysis and haplotype analysis, 46 candidate genes, including five cloned genes, and 49 favorable alleles were identified for these 13 QTL. The effect of the candidate gene Wx on rice elongation difference was validated by a transgenic strategy. These results shed light on the genetic bases of appearance quality and cooked rice elongation and provide gene resources for improving rice quality by molecular breeding.展开更多
Nitrogen(N) deficiency is one of the main factors limiting maize(Zea mays L.) productivity. Genetic improvement of root traits could improve nitrogen use efficiency. An association panel of 461 maize inbred lines was ...Nitrogen(N) deficiency is one of the main factors limiting maize(Zea mays L.) productivity. Genetic improvement of root traits could improve nitrogen use efficiency. An association panel of 461 maize inbred lines was assayed for root growth at seedling emergence under high-nitrate(HN, 5 mmol L^(-1))and low-nitrate(LN, 0.05 mmol L^(-1)) conditions. Twenty-one root traits and three shoot traits were measured. Under LN conditions, the root-to-shoot ratio, root dry weight, total root length, axial root length,and lateral root length on the primary root were all increased. Under LN conditions, the heritability of the plant traits ranged from 0.43 to 0.82, a range much wider than that of 0.27 to 0.55 observed under HN conditions. The panel was genotyped with 542,796 high-density single-nucleotide polymorphism(SNP) markers. Totally 328 significant SNP markers were identified using either mixed linear model(MLM) or general linear model analysis, with 34 detected by both methods. In the 100-kb intervals flanking these SNP markers, four candidate genes were identified. Under LN conditions, the protoporphyrinogen IX oxidase 2 gene was associated with total root surface area and the DELLA protein-encoding gene was associated with the length of the visible lateral root zone of the primary root. Under HN conditions, a histone deacetylase gene was associated with plant height. Under both LN and HN conditions, the gene encoding MA3 domain-containing protein was associated with the first whorl crown root number. The phenotypic and genetic information from this study may be exploited for genetic improvement of root traits aimed at increasing NUE in maize.展开更多
Starch is the most important component in endosperm of sorghum grain.Usually,two types of starch are present:amylose(AM)and amylopectin(AP).The levels of AM and AP contents play a significant role in the appearance,st...Starch is the most important component in endosperm of sorghum grain.Usually,two types of starch are present:amylose(AM)and amylopectin(AP).The levels of AM and AP contents play a significant role in the appearance,structure,and quality of sorghum grains and in marketing applications.In the present study,a panel of 634 sorghum(Sorghum bicolor(L.)Moench)accessions were evaluated for starch,AM,and AP contents of grain,which included a mini core collection of 242 accessions from the International Crops Research Institute for the Semi-Arid Tropics(ICRISAT)in India,and 252 landraces and 140 cultivars from China.The average starch content was 67.64%and the average AM and AP contents were 20.19 and 79.81%,respectively.We developed a total of 260000 high-confidence single nucleotide polymorphism(SNP)markers in the panel of 634 accessions of S.bicolor using specific locus amplified fragment sequencing(SLAF-seq).We performed genome-wide association studies(GWAS)of starch,AM,and AM/AP of grain and SNP markers based on a mixed linear model(MLM).In total,70 significant association signals were detected for starch,AM,and AM/AP ratio of grain with P<4.452×10^-7,of which 10 SNPs were identified with significant starch,51 SNPs were associated with AM,and nine SNPs were associated with the AM/AP ratio.The Gene Ontology(GO)analysis identified 12 candidate genes at five QTLs associated with starch metabolism within the 200-kb intervals,located on chromosomes 1,5,6,and 9.Of these genes,Sobic.006G036500.1 encodes peptidyl-prolyl cis-trans-isomerase CYP38 responsible for hexose monophosphate shunt(HMS)and Sobic.009G071800 encodes 6-phospho-fructokinase(PFK),which is involved in the embden-meyerhof pathway(EMP).Kompetitive allele specific PCR(KASP)markers were developed to validate the GWAS results.The C allele is correlated with a high starch content,while the T allele is linked with a low level of starch content,and provides reliable haplotypes for MAS in sorghum quality improvement.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
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
Wheat grain yield is generally sink-limited during grain filling.The grain-filling rate(GFR)plays a vital role but is poorly studied due to the difficulty of phenotype surveys.This study explored the grain-filling tra...Wheat grain yield is generally sink-limited during grain filling.The grain-filling rate(GFR)plays a vital role but is poorly studied due to the difficulty of phenotype surveys.This study explored the grain-filling traits in a recombinant inbred population and wheat collection using two highly saturated genetic maps for linkage analysis and genome-wide association study(GWAS).Seventeen stable additive quantitative trait loci(QTLs)were identified on chromosomes 1B,4B,and 5A.The linkage interval between IWB19555 and IWB56078 showed pleiotropic effects on GFR_(1),GFR_(max),kernel length(KL),kernel width(KW),kernel thickness(KT),and thousand kernel weight(TKW),with the phenotypic variation explained(PVE)ranging from 13.38%(KW)to 33.69%(TKW).198 significant marker-trait associations(MTAs)were distributed across most chromosomes except for 3D and 4D.The major associated sites for GFR included IWB44469(11.27%),IWB8156(12.56%)and IWB24812(14.46%).Linkage analysis suggested that IWB35850,identified through GWAS,was located in approximately the same region as QGFR_(max)2B.3-11,where two high-confidence candidate genes were present.Two important grain weight(GW)-related QTLs colocalized with grain-filling QTLs.The findings contribute to understanding the genetic architecture of the GFR and provide a basic approach to predict candidate genes for grain yield trait QTLs.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
With recent advances in biotechnology, genome-wide association study (GWAS) has been widely used to identify genetic variants that underlie human complex diseases and traits. In case-control GWAS, typical statistica...With recent advances in biotechnology, genome-wide association study (GWAS) has been widely used to identify genetic variants that underlie human complex diseases and traits. In case-control GWAS, typical statistical strategy is traditional logistical regression (LR) based on single-locus analysis. However, such a single-locus analysis leads to the well-known multiplicity problem, with a risk of inflating type I error and reducing power. Dimension reduction-based techniques, such as principal component-based logistic regression (PC-LR), partial least squares-based logistic regression (PLS-LR), have recently gained much attention in the analysis of high dimensional genomic data. However, the perfor- mance of these methods is still not clear, especially in GWAS. We conducted simulations and real data application to compare the type I error and power of PC-LR, PLS-LR and LR applicable to GWAS within a defined single nucleotide polymorphism (SNP) set region. We found that PC-LR and PLS can reasonably control type I error under null hypothesis. On contrast, LR, which is corrected by Bonferroni method, was more conserved in all simulation settings. In particular, we found that PC-LR and PLS-LR had comparable power and they both outperformed LR, especially when the causal SNP was in high linkage disequilibrium with genotyped ones and with a small effective size in simulation. Based on SNP set analysis, we applied all three methods to analyze non-small cell lung cancer GWAS data.展开更多
Sleepiness affects normal social life, which attracts more and more attention. Circadian phenotypes contribute to obvious individual differences in susceptibility to sleepiness. We aimed to identify candidate single n...Sleepiness affects normal social life, which attracts more and more attention. Circadian phenotypes contribute to obvious individual differences in susceptibility to sleepiness. We aimed to identify candidate single nucleotide polymorphisms(SNPs) which may cause circadian phenotypes, elucidate the potential mechanisms, and generate corresponding SNP-gene-pathways. A genome-wide association studies(GWAS) dataset of circadian phenotypes was utilized in the study. Then, the Identify Candidate Causal SNPs and Pathways analysis was employed to the GWAS dataset after quality control filters. Furthermore, genotype-phenotype association analysis was performed with HapMap database. Four SNPs in three different genes were determined to correlate with usual weekday bedtime,totally providing seven hypothetical mechanisms. Eleven SNPs in six genes were identified to correlate with usual weekday sleep duration, which provided six hypothetical pathways. Our results demonstrated that fifteen candidate SNPs in eight genes played vital roles in six hypothetical pathways implicated in usual weekday bedtime and six potential pathways involved in usual weekday sleep duration.展开更多
Rib eye muscle area(REMA) is an economically important trait and one of the main selection criteria for breeding in the swine industry. In the genome-wide association study(GWAS), the Illumina Porcine SNP60 Bead C...Rib eye muscle area(REMA) is an economically important trait and one of the main selection criteria for breeding in the swine industry. In the genome-wide association study(GWAS), the Illumina Porcine SNP60 Bead Chip containing 62 163 single nucleotide polymorphisms(SNPs) was used to genotype 557 pigs from a porcine Large White×Minzhu intercross population. The REMA(at the 5th–6th, 10th–11th and the last ribs) was measured after slaughtered at the age of(240±7) d for each animal. Association tests between REMA trait and SNPs were performed via the Genome-Wide Rapid Association using the Mixed Model and Regression-Genomic Control(GRAMMAR-GC) approach. From the Ensembl porcine database, SNP annotation was implemented using Sus scrofa Build 10.2. Thirty-three SNPs on SSC12 and 3 SNPs on SSC2 showed significant association with REMA at the last rib at the chromosome-wide significance level. None of the SNPs of REMA at the 5th–6th rib and only a few numbers of the SNPs of REMA at the 10th–11th ribs were found in this study. The Haploview V3.31 program and the Haplo.Stats R package were used to detect and visualize haplotype blocks and to analyze the association of the detected haplotype blocks with REMA at the last rib. A linkage analysis revealed that 4 haplotype blocks contained 4, 4, 2, and 4 SNPs, respectively. Annotations from pig reference genome suggested 2 genes(NOS2, NLK) in block 1(266 kb), one gene(TMIGD1) in block 2(348 kb), and one gene(MAP2K4) in block 3(453 kb). A functional analysis indicated that MYH3 and MYH13 genes are the potential genes controlling REMA at the last rib. We screened several candidate intervals and genes based on the SNPs location and the gene function, and inferred that NOS2 and NLK genes maybe the main genes of REMA at the last ribs.展开更多
基金financially supported by the National Natural Science Foundation of China(32201868 and 32001575)。
文摘Phosphorus(P)is essential for living plants,and P deficiency is one of the key factors limiting the yield in rapeseed production worldwide.As the most important organ for plants,root morphology traits(RMTs)play a key role in P absorption.To investigate the genetic variability of RMT under low P availability,we dissected the genetic structure of RMTs by genome-wide association studies(GWAS),linkage mapping and candidate gene association studies(CGAS).A total of 52 suggestive loci were associated with RMTs under P stress conditions in 405 oilseed rape accessions.The purple acid phosphatase gene BnPAP17 was found to control the lateral root number(LRN)and root dry weight(RDW)under low P stress.The expression of BnPAP17 was increased in shoot tissue in P-efficient cultivars compared to root tissue and P-inefficient cultivars in response to low P stress.Moreover,the haplotype of BnPAP17^(Hap3)was detected for the selective breeding of P efficiency in oilseed rape.Over-expression of the BnPAP17^(Hap3)could promote the shoot and root growth with enhanced tolerance to low P stress and organic phosphorus(Po)utilization in oilseed rape.Collectively,these findings increase our understanding of the mechanisms underlying BnPAP17-mediated low P stress tolerance in oilseed rape.
基金This work was supported by the National Key Research and Development Program of China(2022YFD1200201)Henan Provincial Science and Technology Research and Development Plan Joint Fund(222301420025)the Agricultural Science and Technology Innovation Program(ASTIP)of CAAS.
文摘Nitrogen(N)fertilizer application is essential for crop-plant growth and development.Identifying genetic loci associated with N-use efficiency(NUE)could increase wheat yields and reduce environmental pollution caused by overfertilization.We subjected a panel of 389 wheat accessions to N and chlorate(a nitrate analog)treatments to identify quantitative trait loci(QTL)controlling NUE-associated traits at the wheat seedling stage.Genotyping the panel with a 660K single-nucleotide polymorphism(SNP)array,we identified 397 SNPs associated with N-sensitivity index and chlorate inhibition rate.These SNPs were merged into 49 QTL,of which eight were multi-environment stable QTL and 27 were located near previously reported QTL.A set of 135 candidate genes near the 49 QTL included TaBOX(F-box family protein)and TaERF(ethylene-responsive transcription factor).A Tabox mutant was more sensitive to low-N stress than the wild-type plant.We developed two functional markers for Hap 1,the favorable allele of TaBOX.
基金financially supported by the National Natural Science Foundation of China(Grant No.U20A2032)the Agro ST Project(Grant No.NK2022050102)the Hainan Provincial Natural Science Foundation,China(Grant No.323MS066)。
文摘Rice cooking and eating qualities(CEQ)are mainly determined by cooked rice textural parameters and starch physicochemical properties.However,the genetic bases of grain texture and starch properties in rice have not been fully understood.We conducted a genome-wide association study for apparent amylose content(AAC),starch pasting viscosities,and cooked rice textural parameters using 279 indica rice accessions from the 3000 Rice Genome Project.We identified 26 QTLs in the whole population and detected single nucleotide polymorphisms(SNPs)with the lowest P-value at the Waxy(Wx)locus for all traits except pasting temperature and cohesiveness.Additionally,we detected significant SNPs at the SUBSTANDARD STARCH GRAIN6(SSG6)locus for AAC,setback(SB),hardness,adhesiveness,chewiness(CHEW),gumminess(GUM),and resilience.We subsequently divided the population using a SNP adjacent to the Waxy locus,and identified 23 QTLs and 12 QTLs in two sub-panels,WxT and WxA,respectively.In these sub-panels,SSG6 was also identified to be associated with pasting parameters,including peak viscosity,hot paste viscosity,cold paste viscosity,and consistency viscosity.Furthermore,a candidate gene encoding monosaccharide transporter 5(OsMST5)was identified to be associated with AAC,breakdown,SB,CHEW,and GUM.In total,39 QTLs were co-localized with known genes or previously reported QTLs.These identified genes and QTLs provide valuable information for genetic manipulation to improve rice CEQ.
基金supported by the Xinjiang Uygur Autonomous Region Major Science and Technology Project (2021A02001-3).
文摘Upland cotton(Gossypium hirsutum)is the most important plant producing natural fibers for the textile industry.In this study,we first investigated the phenotypic variation of seven agronomic traits of 273 diverse cotton accessions in the years 2017 and 2018,which were from 18 geographical regions.We found large variations among the traits in different geographical regions and only half of the traits in either years 2017 or 2018 followed a normal distribution.We then genotyped the collection with 81,612 high quality SNPs.Phylogenetic tree and population structure revealed a diverse genetic structure of the core collection,and geographical diversification was an important factor,but account for part of the variances of genetic diversification.We then performed genome-wide association study for the seven traits in the years 2017 and 2018,and the average values of each trait in the two years,respectively.We identified a total of 19 significant marker-trait associations and found that Pollen Ole e 1 allergen/extension could be the candidate gene associated with the fall-off cotton bolls from the last three branches.In addition,large variations were observed for the heritability of traits in the years 2017 and 2018.These results provide new potential candidate genes for further functional validation,which could be useful for genetic improvement and breeding of new cotton cultivars with better agronomic performances.
文摘BACKGROUND John Henryism(JH)is a strategy for dealing with chronic psychological stress characterized by high levels of physical effort and work.Cynicism is a belief that people are motivated primarily by self-interest.High scores on the JH scale and cynicism measures correlate with an increased risk of cardiovascular disease.High cynicism is also a hallmark of burnout syndrome,another known risk factor for heart disease.AIM To evaluate possible interactions between JH and cynicism hoping to clarify risk factors of burnout.METHODS We analyzed genetic and psychological data available from the Database of Genotypes and Phenotypes for genome-wide associations with these traits.We split the total available samples and used plink to perform the association studies on the discovery set(n=1852,80%)and tested for replication using the validation set(n=465).We used scikit-learn to perform supervised machine learning for developing genetic risk algorithms.RESULTS We identified 2,727,and 204 genetic associations for scores on the JH,cynicism and cynical distrust(CD)scales,respectively.We also found 173 associations with high cynicism,109 with high CD,but no associations with high JH.We also produced polygenic classifiers for high cynicism using machine learning with areas under the receiver operator characteristics curve greater than 0.7.CONCLUSION We found significant genetic components to these traits but no evidence of an interaction.Therefore,while there may be a genetic risk,JH is not likely a burnout risk factor.
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.
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.
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.
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funded by the National Key Research and Development Program of China (2016YFD0100301)Project for Cultivating New Transgenic Varieties (2016ZX08009003-004)+2 种基金the Agricultural Science and Technology Innovation Program and the Cooperation and Innovation Mission (CAAS-ZDXT202001)Open Fund of Hubei Collaborative Innovation Center for Grain Industry (HCICGI2020-06)the National Natural Science Foundation of China (U19A2025 and 31870229)。
文摘Appearance and cooked rice elongation are key quality traits of rice. Although some QTL for these traits have been identified, understanding of the genetic relationship between them remains limited. In the present study, large phenotypic variation was observed in 760 accessions from the 3 K Rice Genomes Project for both appearance quality and cooked rice elongation. Most component traits of appearance quality and cooked rice elongation showed significant pairwise correlations, but a low correlation was found between appearance quality and cooked rice elongation. A genome-wide association study identified 74 QTL distributed on all 12 chromosomes for grain length, grain width, length to width ratio, degree of endosperm with chalkiness, rice elongation difference, and elongation index. Thirteen regions containing QTL stably expressed in multiple environments and/or exerting pleiotropic effects on multiple traits were detected. By gene-based association analysis and haplotype analysis, 46 candidate genes, including five cloned genes, and 49 favorable alleles were identified for these 13 QTL. The effect of the candidate gene Wx on rice elongation difference was validated by a transgenic strategy. These results shed light on the genetic bases of appearance quality and cooked rice elongation and provide gene resources for improving rice quality by molecular breeding.
基金supported by the National Natural Science Foundation of China(31672221)。
文摘Nitrogen(N) deficiency is one of the main factors limiting maize(Zea mays L.) productivity. Genetic improvement of root traits could improve nitrogen use efficiency. An association panel of 461 maize inbred lines was assayed for root growth at seedling emergence under high-nitrate(HN, 5 mmol L^(-1))and low-nitrate(LN, 0.05 mmol L^(-1)) conditions. Twenty-one root traits and three shoot traits were measured. Under LN conditions, the root-to-shoot ratio, root dry weight, total root length, axial root length,and lateral root length on the primary root were all increased. Under LN conditions, the heritability of the plant traits ranged from 0.43 to 0.82, a range much wider than that of 0.27 to 0.55 observed under HN conditions. The panel was genotyped with 542,796 high-density single-nucleotide polymorphism(SNP) markers. Totally 328 significant SNP markers were identified using either mixed linear model(MLM) or general linear model analysis, with 34 detected by both methods. In the 100-kb intervals flanking these SNP markers, four candidate genes were identified. Under LN conditions, the protoporphyrinogen IX oxidase 2 gene was associated with total root surface area and the DELLA protein-encoding gene was associated with the length of the visible lateral root zone of the primary root. Under HN conditions, a histone deacetylase gene was associated with plant height. Under both LN and HN conditions, the gene encoding MA3 domain-containing protein was associated with the first whorl crown root number. The phenotypic and genetic information from this study may be exploited for genetic improvement of root traits aimed at increasing NUE in maize.
基金supported by the earmarked fund for China Agriculture Research System (CARS-06)
文摘Starch is the most important component in endosperm of sorghum grain.Usually,two types of starch are present:amylose(AM)and amylopectin(AP).The levels of AM and AP contents play a significant role in the appearance,structure,and quality of sorghum grains and in marketing applications.In the present study,a panel of 634 sorghum(Sorghum bicolor(L.)Moench)accessions were evaluated for starch,AM,and AP contents of grain,which included a mini core collection of 242 accessions from the International Crops Research Institute for the Semi-Arid Tropics(ICRISAT)in India,and 252 landraces and 140 cultivars from China.The average starch content was 67.64%and the average AM and AP contents were 20.19 and 79.81%,respectively.We developed a total of 260000 high-confidence single nucleotide polymorphism(SNP)markers in the panel of 634 accessions of S.bicolor using specific locus amplified fragment sequencing(SLAF-seq).We performed genome-wide association studies(GWAS)of starch,AM,and AM/AP of grain and SNP markers based on a mixed linear model(MLM).In total,70 significant association signals were detected for starch,AM,and AM/AP ratio of grain with P<4.452×10^-7,of which 10 SNPs were identified with significant starch,51 SNPs were associated with AM,and nine SNPs were associated with the AM/AP ratio.The Gene Ontology(GO)analysis identified 12 candidate genes at five QTLs associated with starch metabolism within the 200-kb intervals,located on chromosomes 1,5,6,and 9.Of these genes,Sobic.006G036500.1 encodes peptidyl-prolyl cis-trans-isomerase CYP38 responsible for hexose monophosphate shunt(HMS)and Sobic.009G071800 encodes 6-phospho-fructokinase(PFK),which is involved in the embden-meyerhof pathway(EMP).Kompetitive allele specific PCR(KASP)markers were developed to validate the GWAS results.The C allele is correlated with a high starch content,while the T allele is linked with a low level of starch content,and provides reliable haplotypes for MAS in sorghum quality improvement.
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supported by the National Natural Science Foundation of China (31971936)the Science &Technology Projects of Shandong Province, China (2019YQ028, 2020CXGC010805, 2019B08, 2019YQ014 and ZR2020MC093)
文摘Wheat grain yield is generally sink-limited during grain filling.The grain-filling rate(GFR)plays a vital role but is poorly studied due to the difficulty of phenotype surveys.This study explored the grain-filling traits in a recombinant inbred population and wheat collection using two highly saturated genetic maps for linkage analysis and genome-wide association study(GWAS).Seventeen stable additive quantitative trait loci(QTLs)were identified on chromosomes 1B,4B,and 5A.The linkage interval between IWB19555 and IWB56078 showed pleiotropic effects on GFR_(1),GFR_(max),kernel length(KL),kernel width(KW),kernel thickness(KT),and thousand kernel weight(TKW),with the phenotypic variation explained(PVE)ranging from 13.38%(KW)to 33.69%(TKW).198 significant marker-trait associations(MTAs)were distributed across most chromosomes except for 3D and 4D.The major associated sites for GFR included IWB44469(11.27%),IWB8156(12.56%)and IWB24812(14.46%).Linkage analysis suggested that IWB35850,identified through GWAS,was located in approximately the same region as QGFR_(max)2B.3-11,where two high-confidence candidate genes were present.Two important grain weight(GW)-related QTLs colocalized with grain-filling QTLs.The findings contribute to understanding the genetic architecture of the GFR and provide a basic approach to predict candidate genes for grain yield trait QTLs.
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founded by the National Natural Science Foundation of China(81202283,81473070,81373102 and81202267)Key Grant of Natural Science Foundation of the Jiangsu Higher Education Institutions of China(10KJA330034 and11KJA330001)+1 种基金the Research Fund for the Doctoral Program of Higher Education of China(20113234110002)the Priority Academic Program for the Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine)
文摘With recent advances in biotechnology, genome-wide association study (GWAS) has been widely used to identify genetic variants that underlie human complex diseases and traits. In case-control GWAS, typical statistical strategy is traditional logistical regression (LR) based on single-locus analysis. However, such a single-locus analysis leads to the well-known multiplicity problem, with a risk of inflating type I error and reducing power. Dimension reduction-based techniques, such as principal component-based logistic regression (PC-LR), partial least squares-based logistic regression (PLS-LR), have recently gained much attention in the analysis of high dimensional genomic data. However, the perfor- mance of these methods is still not clear, especially in GWAS. We conducted simulations and real data application to compare the type I error and power of PC-LR, PLS-LR and LR applicable to GWAS within a defined single nucleotide polymorphism (SNP) set region. We found that PC-LR and PLS can reasonably control type I error under null hypothesis. On contrast, LR, which is corrected by Bonferroni method, was more conserved in all simulation settings. In particular, we found that PC-LR and PLS-LR had comparable power and they both outperformed LR, especially when the causal SNP was in high linkage disequilibrium with genotyped ones and with a small effective size in simulation. Based on SNP set analysis, we applied all three methods to analyze non-small cell lung cancer GWAS data.
基金supported by the National Natural Science Foundation of China (No.81470457 and No.81700297)
文摘Sleepiness affects normal social life, which attracts more and more attention. Circadian phenotypes contribute to obvious individual differences in susceptibility to sleepiness. We aimed to identify candidate single nucleotide polymorphisms(SNPs) which may cause circadian phenotypes, elucidate the potential mechanisms, and generate corresponding SNP-gene-pathways. A genome-wide association studies(GWAS) dataset of circadian phenotypes was utilized in the study. Then, the Identify Candidate Causal SNPs and Pathways analysis was employed to the GWAS dataset after quality control filters. Furthermore, genotype-phenotype association analysis was performed with HapMap database. Four SNPs in three different genes were determined to correlate with usual weekday bedtime,totally providing seven hypothetical mechanisms. Eleven SNPs in six genes were identified to correlate with usual weekday sleep duration, which provided six hypothetical pathways. Our results demonstrated that fifteen candidate SNPs in eight genes played vital roles in six hypothetical pathways implicated in usual weekday bedtime and six potential pathways involved in usual weekday sleep duration.
基金supported by the Agricultural Science and Technology Innovation Program,China(ASTIP-IAS02)the National Key Technology R&D Program of China(2011BAD28B01)+3 种基金the National Natural Science Foundation of China(31201781)the National High Technology Re-search and Development Program of China(2011ZX08006-003)the Earmarked Fund for Modern Agro-industry Technology Research System of ChinaChinese Academy of Agricultural Sciences Foundation(2011cj-5)
文摘Rib eye muscle area(REMA) is an economically important trait and one of the main selection criteria for breeding in the swine industry. In the genome-wide association study(GWAS), the Illumina Porcine SNP60 Bead Chip containing 62 163 single nucleotide polymorphisms(SNPs) was used to genotype 557 pigs from a porcine Large White×Minzhu intercross population. The REMA(at the 5th–6th, 10th–11th and the last ribs) was measured after slaughtered at the age of(240±7) d for each animal. Association tests between REMA trait and SNPs were performed via the Genome-Wide Rapid Association using the Mixed Model and Regression-Genomic Control(GRAMMAR-GC) approach. From the Ensembl porcine database, SNP annotation was implemented using Sus scrofa Build 10.2. Thirty-three SNPs on SSC12 and 3 SNPs on SSC2 showed significant association with REMA at the last rib at the chromosome-wide significance level. None of the SNPs of REMA at the 5th–6th rib and only a few numbers of the SNPs of REMA at the 10th–11th ribs were found in this study. The Haploview V3.31 program and the Haplo.Stats R package were used to detect and visualize haplotype blocks and to analyze the association of the detected haplotype blocks with REMA at the last rib. A linkage analysis revealed that 4 haplotype blocks contained 4, 4, 2, and 4 SNPs, respectively. Annotations from pig reference genome suggested 2 genes(NOS2, NLK) in block 1(266 kb), one gene(TMIGD1) in block 2(348 kb), and one gene(MAP2K4) in block 3(453 kb). A functional analysis indicated that MYH3 and MYH13 genes are the potential genes controlling REMA at the last rib. We screened several candidate intervals and genes based on the SNPs location and the gene function, and inferred that NOS2 and NLK genes maybe the main genes of REMA at the last ribs.