Genome-wide microarray-based analysis of miRNAs expression in patients with acute-onchronic liver failure

BACKGROUND: Acute-on-chronic liver failure(ACLF) is a severe clinical syndrome that may cause a high mortality. However, the mechanism is still not clear. Characterization of the microRNA(miRNA) profiles in ACLF patients may provide new clues to the pathogenesis and management of this syndrome. METHODS: Genome-wide microarray was performed to compare the different miRNA expression profiles in peripheral blood mononuclear cells of a pair of monozygotic twins, an ACLF patient and an HBV asymptomatic carrier(AsC). The case-control miRNA profiles were compared and confirmed by quantitative reverse transcription-polymerase chain reaction in 104 ACLF patients and 96 AsCs. A combined computational prediction algorithm was used to predict the potential target genes. RESULTS: Forty-five miRNAs were increased and eight miRNAs were decreased in the ACLF group. The expressions of hsa-let-7a and hsa-miR-16 were increased by 8.58- and 8.63-fold in ACLF patients compared with that in AsCs, respectively(P【0.001). CARD8, BCL2, IL1RAPL1, LTB, FZD10 and EDA were identified as the target genes of hsa-miR-16; MAP4K3, OPRM1, IGF2BP1 and CERCAM were verified as the target genes of hsa-let-7a. CONCLUSIONS: Our results showed that there is a close relationship between specific miRNAs of peripheral blood mononuclear cells and ACLF. hsa-miR-16 and hsa-let-7a may contribute to the development of ACLF.

Genome-Wide Exploration of the Grape GLR Gene Family and Differential Responses of VvGLR3.1 and VvGLR3.2 to Low Temperature and Salt Stress

Grapes,one of the oldest tree species globally,are rich in vitamins.However,environmental conditions such as low temperature and soil salinization significantly affect grape yield and quality.The glutamate receptor(GLR)family,comprising highly conserved ligand-gated ion channels,regulates plant growth and development in response to stress.In this study,11 members of the VvGLR gene family in grapes were identified using whole-genome sequence analysis.Bioinformatic methods were employed to analyze the basic physical and chemical properties,phylogenetic trees,conserved domains,motifs,expression patterns,and evolutionary relationships.Phylogenetic and collinear analyses revealed that the VvGLRs were divided into three subgroups,showing the high conservation of the grape GLR family.These members exhibited 2 glutamate receptor binding regions(GABAb and GluR)and 3-4 transmembrane regions(M1,M2,M3,and M4).Real-time quantitative PCR analysis demonstrated the sensitivity of all VvGLRs to low temperature and salt stress.Subsequent localization studies in Nicotiana tabacum verified that VvGLR3.1 and VvGLR3.2 proteins were located on the cell membrane and cell nucleus.Additionally,yeast transformation experiments confirmed the functionality of VvGLR3.1 and VvGLR3.2 in response to low temperature and salt stress.Thesefindings highlight the significant role of the GLR family,a highly conserved group of ion channels,in enhancing grape stress resistance.This study offers new insights into the grape GLR gene family,providing fundamental knowledge for further functional analysis and breeding of stress-resistant grapevines.

Assessing the conservation impact of Chinese indigenous chicken populations between ex-situ and in-situ using genome-wide SNPs

Conservation programs require rigorous evaluation to ensure the preservation of genetic diversity and viability of conservation populations. In this study, we conducted a comparative analysis of two indigenous Chinese chicken breeds, Gushi and Xichuan black-bone, using whole-genome SNPs to understand their genetic diversity, track changes over time and population structure. The breeds were divided into five conservation populations(GS1, 2010, ex-situ;GS2, 2019, ex-situ;GS3, 2019, in-situ;XB1, 2010, in-situ;and XB2, 2019, in-situ) based on conservation methods and generations. The genetic diversity indices of three conservation populations of Gushi chicken showed consistent trends, with the GS3 population under in-situ strategy having the highest diversity and GS2 under ex-situ strategy having the lowest. The degree of inbreeding of GS2 was higher than that of GS1 and GS3. Conserved populations of Xichuan black-bone chicken showed no obvious changes in genetic diversity between XB1 and XB2. In terms of population structure, the GS3 population were stratified relative to GS1 and GS2. According to the conservation priority, GS3 had the highest contribution to the total gene and allelic diversity in GS breed, whereas the contribution of XB1 and XB2 were similar. We also observed that the genetic diversity of GS2 was lower than GS3, which were from the same generation but under different conservation programs(in-situ and ex-situ). While XB1 and XB2 had similar levels of genetic diversity. Overall, our findings suggested that the conservation programs performed in ex-situ could slow down the occurrence of inbreeding events, but could not entirely prevent the loss of genetic diversity when the conserved population size was small, while in-situ conservation populations with large population size could maintain a relative high level of genetic diversity.

Epistasis-aware genome-wide association studies provide insights into the efficient breeding of high-yield and high-quality rice

Marker-assisted selection(MAS)and genomic selection(GS)breeding have greatly improved the efficiency of rice breeding.Due to the influences of epistasis and gene pleiotropy,ensuring the actual breeding effect of MAS and GS is still a difficult challenge to overcome.In this study,113 indica rice varieties(V)and their 565 testcross hybrids(TC)were used as the materials to investigate the genetic basis of 12 quality traits and nine agronomic traits.The original traits and general combining ability of the parents,as well as the original traits and midparent heterosis of TC,were subjected to genome-wide association analysis.In total,381 primary significantly associated loci(SAL)and 1,759 secondary SALs that had epistatic interactions with these primary SALs were detected.Among these loci,322 candidate genes located within or nearby the SALs were screened,204 of which were cloned genes.A total of 39 MAS molecular modules that are beneficial for trait improvement were identified by pyramiding the superior haplotypes of candidate genes and desirable epistatic alleles of the secondary SALs.All the SALs were used to construct genetic networks,in which 91 pleiotropic loci were investigated.Additionally,we estimated the accuracy of genomic prediction in the parent V and TC by incorporating either no SALs,primary SALs,secondary SALs or epistatic effect SALs as covariates.Although the prediction accuracies of the four models were generally not significantly different in the TC dataset,the incorporation of primary SALs,secondary SALs,and epistatic effect SALs significantly improved the prediction accuracies of 5(26%),3(16%),and 11(58%)traits in the V dataset,respectively.These results suggested that SALs and epistatic effect SALs identified based on an additive genotype can provide considerable predictive power for the parental lines.They also provide insights into the genetic basis of complex traits and valuable information for molecular breeding in rice.

Leveraging the potential of big genomic and phenotypic data for genome-wide association mapping in wheat

Genome-wide association mapping studies(GWAS)based on Big Data are a potential approach to improve marker-assisted selection in plant breeding.The number of available phenotypic and genomic data sets in which medium-sized populations of several hundred individuals have been studied is rapidly increasing.Combining these data and using them in GWAS could increase both the power of QTL discovery and the accuracy of estimation of underlying genetic effects,but is hindered by data heterogeneity and lack of interoperability.In this study,we used genomic and phenotypic data sets,focusing on Central European winter wheat populations evaluated for heading date.We explored strategies for integrating these data and subsequently the resulting potential for GWAS.Establishing interoperability between data sets was greatly aided by some overlapping genotypes and a linear relationship between the different phenotyping protocols,resulting in high quality integrated phenotypic data.In this context,genomic prediction proved to be a suitable tool to study relevance of interactions between genotypes and experimental series,which was low in our case.Contrary to expectations,fewer associations between markers and traits were found in the larger combined data than in the individual experimental series.However,the predictive power based on the marker-trait associations of the integrated data set was higher across data sets.Therefore,the results show that the integration of medium-sized to Big Data is an approach to increase the power to detect QTL in GWAS.The results encourage further efforts to standardize and share data in the plant breeding community.

Genome-Wide Association Study of Cooked Rice Textural Attributes and Starch Physicochemical Properties in indica Rice

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.

Genome-wide association study of seedling nitrogen-use efficiency-associated traits in common wheat(Triticum aestivum L.)

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.

Genome-Wide Analysis for Yield-Related Agronomic and Biochemical Traits of Chinese and Bangladeshi Grass Pea Genotypes Using SSR Markers

Grass pea(Lathyrus sativus L.)is an imperative food crop cultured in dryland agricultural ecology.It is a vital source of dietary protein to millions of populaces living in low-income countries in South-East Asia and Africa.This study highlights the improvement of genomic properties and their application in marker-trait relationships for 17 yield-related characters in 400 grass pea genotypes from China and Bangladesh.These characters were assessed via 56 polymorphic markers using general linear model(GLM)(P+G+Q)and mixed linear model(MLM)(P+G+Q+K)in the tassel software based on the linkage disequilibrium and population structure analysis.Population structure analysis showed two major groups and one admixed group in the populace.Statistically significant loci pairs of linkage disequilibrium(LD)mean value(D′)was 0.479.A total of 99 and 61 marker-trait associations in GLM and MLM models allied to the 17 traits were accepted at a 5%level of significance.Among these markers,21 markers were associated with more than one trait;12 marker-trait associations passed the Bonferroni correction threshold.Both models found six markers C41936,C39067,C34100,C47146,C47638,and C43047 significantly associated with days to maturity,flower color,plant height,and seed per pod were detected in the Hebei and Liaoyang location(p≤0.01),and the interpretation rate(R^(2)value)11.2%to 43.6%.Conferring to the consequences,the association analysis methodology may operative system for quantitative,qualitative,and biochemical traits related to gene position mapping and support breeders in improving novel approaches for advancing the grass pea quality.

Genome-wide association mapping and genomic prediction of stalk rot in two mid-altitude tropical maize populations

Maize stalk rot reduces grain yield and quality.Information about the genetics of resistance to maize stalk rot could help breeders design effective breeding strategies for the trait.Genomic prediction may be a more effective breeding strategy for stalk-rot resistance than marker-assisted selection.We performed a genome-wide association study(GWAS)and genomic prediction of resistance in testcross hybrids of 677 inbred lines from the Tuxpe?o and non-Tuxpe?o heterotic pools grown in three environments and genotyped with 200,681 single-nucleotide polymorphisms(SNPs).Eighteen SNPs associated with stalk rot shared genomic regions with gene families previously associated with plant biotic and abiotic responses.More favorable SNP haplotypes traced to tropical than to temperate progenitors of the inbred lines.Incorporating genotype-by-environment(G×E)interaction increased genomic prediction accuracy.

Genome-Wide Discovery and Expression Profiling of the SWEET Sugar Transporter Gene Family in Woodland Strawberry (Fragaria vesca) under Developmental and Stress Conditions: Structural and Evolutionary Analysis

The SWEET(sugar will eventually be exported transporter)family proteins are a recently identified class of sugar transporters that are essential for various physiological processes.Although the functions of the SWEET proteins have been identified in a number of species,to date,there have been no reports of the functions of the SWEET genes in woodland strawberries(Fragaria vesca).In this study,we identified 15 genes that were highly homolo-gous to the A.thaliana AtSWEET genes and designated them as FvSWEET1–FvSWEET15.We then conducted a structural and evolutionary analysis of these 15 FvSWEET genes.The phylogenetic analysis enabled us to categor-ize the predicted 15 SWEET proteins into four distinct groups.We observed slight variations in the exon‒intron structures of these genes,while the motifs and domain structures remained highly conserved.Additionally,the developmental and biological stress expression profiles of the 15 FvSWEET genes were extracted and analyzed.Finally,WGCNA coexpression network analysis was run to search for possible interacting genes of FvSWEET genes.The results showed that the FvSWEET10 genes interacted with 20 other genes,playing roles in response to bacterial and fungal infections.The outcomes of this study provide insights into the further study of FvSWEET genes and may also aid in the functional characterization of the FvSWEET genes in woodland strawberries.

Genome-wide and candidate gene association studies identify BnPAP17 as conferring the utilization of organic phosphorus in oilseed rape

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.

Genetic Parameters and Genome-Wide Association Studies for Body Size Traits of Shuxuan Cattle in China

In domestic cattle,the body size traits have important implications in terms of breed characteristics and production performance.Shuxuan cattle is a dual-purpose breed mainly raised in Sichuan province,China,for which we have known less about the genetic parameters and underlying candidate genes in relation to the body size traits.In this study,we obtained the genome-wide single nucleotide polymorphisms(SNPs)using the Illumina Bovine BeadChip in 275 Shuxuan cattle.These SNPs were first used for estimating genetic parameters for the withers height(WH)and diagonal body length(BL).Using the bivariate animal model,the estimates(±standard error)of heritabilities were 0.71±0.22 and 0.49±0.29 for BL,and their genetic correlation was 0.64±0.37.Second,the genome-wide association study(GWAS)was performed.However,these did not result into genome-wide significant SNPs for both WH and BL traits.According to a less stringent suggestive significance,some positional candidate genes were found,and some of them(such as FAM110B,TAS1R2,PAX3,and FHIT)were previously reported in literature to be associated with body size traits in cattle.In conclusion,we estimated the genetic parameters in Shuxuan cattle using genomic information for the first time,which are required for implementing the genomic selection programs in the future.

Genome-wide identification of gene expression in the epididymis of infertile rat induced by alpha-chlorohydrin using oligonucleotide microarray

Objective To establish a rat model of sterility associated with epididymis and epididymal gene expression profiles relation to fertility by alpha-chlorohydrin.Methods Rats were treated with 10 mg·kg-1·d-1.alpha-chlorohydrin for 10 consecutive days.Sperm maturation and other fertility parameters were analyzed.The sperm motility and morphology were evaluated by computer-assisted sperm analysis(CASA);sperm survival rate was assessed by SYBR-14 and propidium iodide(PI)fluorescent staining;the weights of testes,epididymides,prostates and seminal vesicles were determined by electronic balance;histological examination of above tissues were evaluated by HE staining;and serumal dihydrotestosterone(DHT)and testosterone(T)of rats were detected by enzyme-labeled immunoassay.Each male rat was paired with 2 female rats in proestrus.Female rats were examined the next morning for the presence of sperm in vaginal smears and underwent a cesarean section on day 12 of gestation.Finally the reproductive indices were calculated as follows:copulation index(number of sperm positive females /number of pairings),pregnancy index(number of pregnancies /number of sperm positive females),and fertility index(number of pregnancies /number of pairings).After that we used Affymetrix Rat 230 2.0 oligo-microarray to identify epididymal special genes associated with fertility.Finally,we validated some of these genes by Real-Time quantitative polymerase chain reaction.Results The motility of spermatozoa from the cauda epididymidis of treated rats showed a significant decrease in percentage of motile,progressively motile sperm,and sperm survival rate.At the same time,the morphology of cauda epididymal spermatozoa was also adversely affected by the treatment.In addition,the serumal androgen levels of treated animals weren't changed compared with the control group.Accordingly,matings with treated males resulted in no successful pregnancy.Then,we classified general functions of the down or up regulated epididymal genes by chlorhydrin with the GeneSpring gene ontology(GO)analysis,which are involved in macromolecular metabolism and transport,primary metabolism process,cell metabolism,biological process regulation,immunology regulation,ion combination,hydratase and oxidoreductase activity.Among all the different expressed genes,we analyzed and screened the down-regulated genes associated with glucose,lipid,protein and other energy metabolism,which are considered as the major ACH action targets.Simultaneously,the up-regulated genes by chlorhydrin were detected and their characters of negative regulated sperm maturation and fertility analyzed,which are apoptosis and immune-related genes and not reported before.Conclusions We established male infertile rat model with ACH(10 mg·kg-1·d-1,po,10 days)through evaluating changes of sperm motility and morphology,mating index,fertility index and pregnancy index.Simultaneously,the ACH didn't affect the major androgen(T and DHT)metabolism and sexual ability,which is considered as the best way for male contraception.Then we determined the down-regulated epididymal genes relation to substance metabolism,which can affect the epididymal sperm maturation and presumed the major antifertility targets by ACH.Further more,we found and analyzed the epididymal up-regulated genes associated with apoptosis and immune functions,which maybe the new possible sites of action by ACH and other male antifertility agents.

Genome-Wide Transcriptional Analysis of Yield and Heterosis-Associated Genes in Maize (Zea mays L.)

Heterosis has contributed greatly to yield in maize, but the nature of its contribution is not completely clear. In this study, two strategies using whole-genome oligonucleotide microarrays were employed to identify differentially expressed genes （DEGs） associated with heterosis and yield. The analysis revealed 1 838 heterosis-associated genes （HAGs）, 265 yield- associated genes （YAGs）, and 85 yield heterosis-associated genes （YHAGs）. 37.1% of HAGs and 22.4% of YHAGs expressed additively. The remaining genes expressed non-additively, including those with high/low-parent dominance and over/under dominance, which were prevalent in this research. Pathway enrichment analysis and quantitative trait locus （QTL） co-mapping demonstrated that the metabolic pathways for energy and carbohydrates were the two main enriched pathways influencing heterosis and yield. Therefore, the DEGs participating in energy and carbohydrate metabolism were considered to contribute to heterosis and yield significantly. The investigation of potential groups of HAGs, YAGs, and YHAGs might provide valuable information for exploiting heterosis to improve yield in maize breeding. In addition, our results support the view that heterosis is contributed by multiple, complex molecular mechanisms.

Genome-wide association study for starch content and constitution in sorghum(Sorghum bicolor(L.) Moench)

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.

Genome-wide association study of vitamin E in sweet corn kernels

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.

Genetic polymorphisms and gastric cancer risk: a comprehensive review synopsis from meta-analysis and genome-wide association studies

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.

Implications of discoveries from genome-wide association studies in current cardiovascular practice

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.

Myopia genetics in genome-wide association and postgenome-wide association study era

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.

Genome-wide association study and genomic prediction of Fusarium ear rot resistance in tropical maize germplasm

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.