We conducted a genome-wide linkage scan and positional association study to identify genes and variants influencing blood lipid levels among participants of the Genetic Epidemiology Network of Salt-Sensitivity （GenS...We conducted a genome-wide linkage scan and positional association study to identify genes and variants influencing blood lipid levels among participants of the Genetic Epidemiology Network of Salt-Sensitivity （GenSalt） study. The GenSalt study was conducted among 1906 participants from 633 Han Chinese families. Lipids were measured from overnight fasting blood samples using standard methods. Multipoint quantitative trait genome-wide linkage scans were performed on the high-density lipoprotein, low-density lipoprotein, and log- transformed triglyceride phenotypes. Using dense panels of single nucleotide polymorphisms （SNPs）, single-marker and gene-based association analyses were conducted to follow-up on promising linkage signals. Additive associations between each SNP and lipid phenotypes were tested using mixed linear regression models. Gene-based analyses were performed by combining P-values from single- marker analyses within each gene using the truncated product method （TPM）. Significant associations were assessed for replication among 777 Asian participants of the Multi-ethnic Study of Atherosclerosis （MESA）. Bonferroni correction was used to adjust for multiple testing. In the GenSalt study, suggestive linkage signals were identified at 2p11.2-2q12.1 [maximum multipoint LOD score （MML） = 2.18 at 2q11.2] and t lq24.3-11q25 （MML = 2.29 at 11q25） for the log-transformed triglyceride phenotype. Follow-up analyses of these two regions revealed gene-based associations of charged multivesicular body protein 3 （CHMP3）, ring finger protein 103 （RNF103）, AF4/FMR2 family, member 3 （AFF3）, and neurotrirnin （NTM） with triglycerides （P = 4 ×10^-4, 1.00 × 10^-5, 2.00 × 10^-5, and 1.00 × 10^-7, respectively）. Both the AFF3 and NTM triglyceride associations were replicated among MESA study participants（P = 1.00 × 10^-7 and 8.00× 10^-5, respectively）. Furthermore, NTM explained the linkage signal on chromosome 11, In conclusion, we identified novel genes associated with lipid phenotypes in linkage regions on chromosomes 2 and 11.展开更多
Barley(Hordeum vulgare L.)ranks as the fourth most cultivated cereal crop globally by planting area.Kernel characteristics,including grain length,grain width,and thousand-grain weight(TGW),are essential determinants o...Barley(Hordeum vulgare L.)ranks as the fourth most cultivated cereal crop globally by planting area.Kernel characteristics,including grain length,grain width,and thousand-grain weight(TGW),are essential determinants of barley yield and quality.The identification and cloning of genes related to kernel traits,along with the detection of superior alleles,are fundamental for marker-assisted selection in barley breeding.This study presents the cloning of HvGL7-2H from barley,based on the known rice GL7 gene.The functional significance of HvGL7-2H in grain length was confirmed through ethyl methane sulfonate(EMS)mutants of the barley landrace“Hatiexi”.A candidate gene-based association analysis was conducted using a panel of 363 barley accessions to identify superior haplotypes for HvGL7-2H.The analysis revealed that Hap3 represented the superior haplotype for both grain length and TGW,while Hap4 emerged as the superior haplotype for TGW.These findings indicate that genotypes carrying the superior allele serve as valuable genetic resources,and the molecular markers identified herein will facilitate grain size and yield improvement in barley breeding programs.展开更多
The rapid development of multiome(transcriptome,proteome,cistrome,imaging,and regulome)-wide association study methods have opened new avenues for biologists to understand the susceptibility genes underlying complex d...The rapid development of multiome(transcriptome,proteome,cistrome,imaging,and regulome)-wide association study methods have opened new avenues for biologists to understand the susceptibility genes underlying complex diseases.Thorough comparisons of these methods are essential for selecting the most appropriate tool for a given research objective.This review provides a detailed categorization and summary of the statistical models,use cases,and advantages of recent multiome-wide association studies.In addition,to illustrate gene-disease association studies based on transcriptome-wide association study(TWAS),we collected 478 disease entries across 22 categories from 235 manually reviewed publications.Our analysis reveals that mental disorders are the most frequently studied diseases by TWAS,indicating its potential to deepen our understanding of the genetic architecture of complex diseases.In summary,this review underscores the importance of multiome-wide association studies in elucidating complex diseases and highlights the significance of selecting the appropriate method for each study.展开更多
基金supported by a cooperative agreement project grant (Nos. U01HL072507,R01HL087263,and R01HL090682) from the National Heart,Lung,and Blood Institute (NHLBI),National Institutes of Health,Bethesda,MDsupported by a career development award (No. K08HL091108) from NHLBI+2 种基金supported by NHLBI in collaboration with MESA investigatorsprovided by contracts N01-HC-95159,N01-HC95160,N01-HC-95161,N01-HC-95162,N01-HC-95163,N01HC-95164,N01-HC-95165,N01-HC-95166,N01-HC-95167,N01-HC-95168,N01-HC-95169 and CTSA UL1-RR-024156provided by NHLBI Contract N02-HL-64278
文摘We conducted a genome-wide linkage scan and positional association study to identify genes and variants influencing blood lipid levels among participants of the Genetic Epidemiology Network of Salt-Sensitivity （GenSalt） study. The GenSalt study was conducted among 1906 participants from 633 Han Chinese families. Lipids were measured from overnight fasting blood samples using standard methods. Multipoint quantitative trait genome-wide linkage scans were performed on the high-density lipoprotein, low-density lipoprotein, and log- transformed triglyceride phenotypes. Using dense panels of single nucleotide polymorphisms （SNPs）, single-marker and gene-based association analyses were conducted to follow-up on promising linkage signals. Additive associations between each SNP and lipid phenotypes were tested using mixed linear regression models. Gene-based analyses were performed by combining P-values from single- marker analyses within each gene using the truncated product method （TPM）. Significant associations were assessed for replication among 777 Asian participants of the Multi-ethnic Study of Atherosclerosis （MESA）. Bonferroni correction was used to adjust for multiple testing. In the GenSalt study, suggestive linkage signals were identified at 2p11.2-2q12.1 [maximum multipoint LOD score （MML） = 2.18 at 2q11.2] and t lq24.3-11q25 （MML = 2.29 at 11q25） for the log-transformed triglyceride phenotype. Follow-up analyses of these two regions revealed gene-based associations of charged multivesicular body protein 3 （CHMP3）, ring finger protein 103 （RNF103）, AF4/FMR2 family, member 3 （AFF3）, and neurotrirnin （NTM） with triglycerides （P = 4 ×10^-4, 1.00 × 10^-5, 2.00 × 10^-5, and 1.00 × 10^-7, respectively）. Both the AFF3 and NTM triglyceride associations were replicated among MESA study participants（P = 1.00 × 10^-7 and 8.00× 10^-5, respectively）. Furthermore, NTM explained the linkage signal on chromosome 11, In conclusion, we identified novel genes associated with lipid phenotypes in linkage regions on chromosomes 2 and 11.
基金financially supported by the National Natural Science Foundation of China(31771774)the National Key Research and Development Program of China(2018YFD1000700 and 2018YFD1000706)+1 种基金the Young Top-notch Talent Cultivation Program of Hubei Province,Hubei Hongshan Laboratory,Chinathe China Agriculture Research System of Ministry of Agriculture and Rural Affairs(CARS-05).
文摘Barley(Hordeum vulgare L.)ranks as the fourth most cultivated cereal crop globally by planting area.Kernel characteristics,including grain length,grain width,and thousand-grain weight(TGW),are essential determinants of barley yield and quality.The identification and cloning of genes related to kernel traits,along with the detection of superior alleles,are fundamental for marker-assisted selection in barley breeding.This study presents the cloning of HvGL7-2H from barley,based on the known rice GL7 gene.The functional significance of HvGL7-2H in grain length was confirmed through ethyl methane sulfonate(EMS)mutants of the barley landrace“Hatiexi”.A candidate gene-based association analysis was conducted using a panel of 363 barley accessions to identify superior haplotypes for HvGL7-2H.The analysis revealed that Hap3 represented the superior haplotype for both grain length and TGW,while Hap4 emerged as the superior haplotype for TGW.These findings indicate that genotypes carrying the superior allele serve as valuable genetic resources,and the molecular markers identified herein will facilitate grain size and yield improvement in barley breeding programs.
基金supported by the National Natural Science Foundation of China(Grant Nos.62102068,62231013,61821002,81971750,81701833)the National Key R&D Program of China(Grant No.2017YFA0104300).
文摘The rapid development of multiome(transcriptome,proteome,cistrome,imaging,and regulome)-wide association study methods have opened new avenues for biologists to understand the susceptibility genes underlying complex diseases.Thorough comparisons of these methods are essential for selecting the most appropriate tool for a given research objective.This review provides a detailed categorization and summary of the statistical models,use cases,and advantages of recent multiome-wide association studies.In addition,to illustrate gene-disease association studies based on transcriptome-wide association study(TWAS),we collected 478 disease entries across 22 categories from 235 manually reviewed publications.Our analysis reveals that mental disorders are the most frequently studied diseases by TWAS,indicating its potential to deepen our understanding of the genetic architecture of complex diseases.In summary,this review underscores the importance of multiome-wide association studies in elucidating complex diseases and highlights the significance of selecting the appropriate method for each study.
