scholarly journals TWAS results are complementary to and less affected by linkage disequilibrium than GWAS

2021 ◽  
Author(s):  
Delin Li ◽  
Qiang Liu ◽  
Patrick S Schnable
Keyword(s):  
Linkage Disequilibrium ◽  
Association Study ◽  
Phenotypic Variation ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Expression Levels ◽  
Genome Wide ◽  
A Genome ◽  
Gene Level ◽  
Gene Expression Levels

Abstract A genome-wide association study (GWAS) is used to identify genetic markers associated with phenotypic variation. In contrast, a transcriptome-wide association study (TWAS) detects associations between gene expression levels and phenotypic variation. It has previously been shown that in the cross-pollinated species, maize (Zea mays), GWAS and TWAS identify complementary sets of trait-associated genes, many of which exhibit characteristics of true positives. Here, we extend this conclusion to the self-pollinated species, Arabidopsis thaliana and soybean (Glycine max). Linkage disequilibrium (LD) can result in the identification, via GWAS, of false-positive associations. In all three analyzed plant species, most trait-associated genes identified via TWAS are well separated physically from other candidate genes. Hence, TWAS is less affected by LD than is GWAS, demonstrating that TWAS is particularly well suited for association studies in genomes with slow rates of LD decay, such as soybean. TWAS is reasonably robust to the plant organs/tissues used to determine expression levels. In summary, this study confirms that TWAS is a promising approach for accurate gene-level association mapping in plants that is complementary to GWAS, and established that TWAS can exhibit substantial advantages relative to GWAS in species with slow rates of LD decay.

scholarly journals Genome-Wide Association Study and Selection Signatures Detect Genomic Regions Associated with Seed Yield and Oil Quality in Flax

2018 ◽  
Vol 19 (8) ◽  
pp. 2303 ◽  
Author(s):  
Frank You ◽  
Jin Xiao ◽  
Pingchuan Li ◽  
Zhen Yao ◽  
Gaofeng Jia ◽  
...  
Keyword(s):  
Association Study ◽  
Seed Yield ◽  
Phenotypic Variation ◽  
Genome Wide Association Study ◽  
Oil Quality ◽  
Genome Wide Association ◽  
Selection Signatures ◽  
Genome Wide ◽  
A Genome ◽  
Genomic Regions

A genome-wide association study (GWAS) was performed on a set of 260 lines which belong to three different bi-parental flax mapping populations. These lines were sequenced to an averaged genome coverage of 19× using the Illumina Hi-Seq platform. Phenotypic data for 11 seed yield and oil quality traits were collected in eight year/location environments. A total of 17,288 single nucleotide polymorphisms were identified, which explained more than 80% of the phenotypic variation for days to maturity (DTM), iodine value (IOD), palmitic (PAL), stearic, linoleic (LIO) and linolenic (LIN) acid contents. Twenty-three unique genomic regions associated with 33 quantitative trait loci (QTL) for the studied traits were detected, thereby validating four genomic regions previously identified. The 33 QTL explained 48–73% of the phenotypic variation for oil content, IOD, PAL, LIO and LIN but only 8–14% for plant height, DTM and seed yield. A genome-wide selective sweep scan for selection signatures detected 114 genomic regions that accounted for 7.82% of the flax pseudomolecule and overlapped with the 11 GWAS-detected genomic regions associated with 18 QTL for 11 traits. The results demonstrate the utility of GWAS combined with selection signatures for dissection of the genetic structure of traits and for pinpointing genomic regions for breeding improvement.

P1-229: Genome-Wide Association Study of Brain Gene Expression Levels (eGWAS)

2011 ◽  
Vol 7 ◽  
pp. S184-S184
Author(s):  
Nilufer Ertekin-Taner ◽  
Fanggeng Zou ◽  
High Chai ◽  
Curtis Younkin ◽  
Julia Crook ◽  
...  
Keyword(s):  
Gene Expression ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Expression Levels ◽  
Brain Gene Expression ◽  
Genome Wide ◽  
Gene Expression Levels

scholarly journals Panton-Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial genome-wide association study

2018 ◽  
Author(s):  
Bernadette C Young ◽  
Sarah G Earle ◽  
Sona Soeng ◽  
Poda Sar ◽  
Varun Kumar ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Bacterial Genome ◽  
Strong Relationship ◽  
Genome Wide Association ◽  
Tropical Regions ◽  
Genome Wide ◽  
A Genome

AbstractPyomyositis is a severe bacterial infection of skeletal muscle, commonly affecting children in tropical regions and predominantly caused by Staphylococcus aureus. To understand the contribution of bacterial genomic factors to pyomyositis, we conducted a genome-wide association study of S. aureus cultured from 101 children with pyomyositis and 417 children with asymptomatic nasal carriage attending the Angkor Hospital for Children in Cambodia. We found a strong relationship between bacterial genetic variation and pyomyositis, with estimated heritability 63.8% (95% CI 49.2-78.4%). The presence of the Panton-Valentine leucocidin (PVL) locus increased the odds of pyomyositis 130-fold (p =10-17.9). The signal of association mapped both to the PVL-coding sequence and the sequence immediately upstream. Together these regions explained > 99.9% of heritability. Our results establish staphylococcal pyomyositis, like tetanus and diphtheria, as critically dependent on expression of a single toxin and demonstrate the potential for association studies to identify specific bacterial genes promoting severe human disease.

scholarly journals Genome-Wide Association Study and Selection Signatures Detect Genomic Regions Associated with Seed Yield and Oil Quality in Flax

2018 ◽  
Author(s):  
Frank You ◽  
Jin Xiao ◽  
Pingchuan Li ◽  
Zhen Yao ◽  
Gaofeng Jia ◽  
...  
Keyword(s):  
Association Study ◽  
Seed Yield ◽  
Phenotypic Variation ◽  
Genome Wide Association Study ◽  
Oil Quality ◽  
Genome Wide Association ◽  
Selection Signatures ◽  
Genome Wide ◽  
A Genome ◽  
Genomic Regions

A genome-wide association study (GWAS) was performed on a set of 260 lines which belong to three different bi-parental flax mapping populations. These lines were sequenced to an averaged genome coverage of 19× using the Illumina Hi-Seq platform. Phenotypic data for 11 seed yield and oil quality traits were collected in eight year/location environments. A total of 17,288 single nucleotide polymorphisms were identified, which explained more than 80% of the phenotypic variation for days to maturity (DTM), iodine value (IOD), palmitic (PAL), stearic, linoleic (LIO) and linolenic (LIN) acid contents. Twenty-three unique genomic regions associated with 33 QTL for the studied traits were detected, thereby validating four genomic regions previously identified. The 33 QTL explained 48-73% of the phenotypic variation for oil content, IOD, PAL, LIO and LIN but only 8-14% for plant height, DTM and seed yield. A genome-wide selective sweep scan for selection signatures detected 114 genomic regions that accounted for 7.82% of the flax pseudomolecule and overlapped with the 11 GWAS-detected genomic regions associated with 18 QTL for 11 traits. The results demonstrate the utility of GWAS combined with selection signatures for dissection of the genetic structure of traits and for pinpointing genomic regions for breeding improvement.

scholarly journals Genome-Wide Association Study and Pathway Analysis for Heterophil/Lymphocyte (H/L) Ratio in Chicken

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1005
Author(s):  
Jie Wang ◽  
Bo Zhu ◽  
Jie Wen ◽  
Qinghe Li ◽  
Guiping Zhao
Keyword(s):  
Association Study ◽  
Pathway Analysis ◽  
Phenotypic Variation ◽  
Genome Wide Association Study ◽  
Genetic Regulation ◽  
Genetic Selection ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
A Genome

Disease control and prevention have been critical factors in the dramatic growth of the poultry industry. Disease resistance in chickens can be improved through genetic selection for immunocompetence. The heterophil/lymphocyte ratio (H/L) in the blood reflects the immune system status of chickens. Our objective was to conduct a genome-wide association study (GWAS) and pathway analysis to identify possible biological mechanisms involved in H/L traits. In this study, GWAS for H/L was performed in 1317 Cobb broilers to identify significant single-nucleotide polymorphisms (SNPs) associated with H/L. Eight SNPs (p < 1/8068) reached a significant level of association. The significant SNP on GGA 19 (chicken chromosome 19) was in the gene for complement C1q binding protein (C1QBP). The wild-type and mutant individuals showed significant differences in H/L at five identified SNPs (p < 0.05). According to the results of pathway analysis, nine associated pathways (p < 0.05) were identified. By combining GWAS with pathway analysis, we found that all SNPs after QC explained 12.4% of the phenotypic variation in H/L, and 52 SNPs associated with H/L explained as much as 9.7% of the phenotypic variation in H/L. Our findings contribute to understanding of the genetic regulation of H/L and provide theoretical support.

scholarly journals Genome-Wide Association Study and Selection Signatures Detect Genomic Regions Associated with Seed Yield and Oil Quality in Flax

2018 ◽  
Author(s):  
Frank You ◽  
Jin Xiao ◽  
Pingchuan Li ◽  
ZHEN YAO ◽  
Gaofeng Jia ◽  
...  
Keyword(s):  
Association Study ◽  
Seed Yield ◽  
Phenotypic Variation ◽  
Genome Wide Association Study ◽  
Oil Quality ◽  
Genome Wide Association ◽  
Selection Signatures ◽  
Genome Wide ◽  
A Genome ◽  
Genomic Regions

A genome-wide association study (GWAS) was performed on a set of 260 lines which belong to three different bi-parental flax mapping populations. These lines were sequenced to an averaged genome coverage of 19&times; using the Illumina Hi-Seq platform. Phenotypic data for 11 seed yield and oil quality traits were collected in eight year/location environments. A total of 17,288 single nucleotide polymorphisms were identified, which explained more than 80% of the phenotypic variation for days to maturity (DTM), iodine value (IOD), palmitic (PAL), stearic, linoleic (LIO) and linolenic (LIN) acid contents. Twenty-three unique genomic regions associated with 33 QTL for the studied traits were detected, thereby validating four genomic regions previously identified. The 33 QTL explained 48-73% of the phenotypic variation for oil content, IOD, PAL, LIO and LIN but only 8-14% for plant height, DTM and seed yield. A genome-wide selective sweep scan for selection signatures detected 114 genomic regions that accounted for 7.82% of the flax pseudomolecule and overlapped with the 11 GWAS-detected genomic regions associated with 18 QTL for 11 traits. The results demonstrate the utility of GWAS combined with selection signatures for dissection of the genetic structure of traits and for pinpointing genomic regions for breeding improvement.

scholarly journals GENOME-WIDE ASSOCIATION STUDY OF EXTREME HUMAN LONGEVITY DISCOVERS UNCOMMON LONGEVITY VARIANTS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S209-S209
Author(s):  
Anastasia Gurinovich ◽  
Anastasia Gurinovich ◽  
Zeyuan Song ◽  
Stacy L Andersen ◽  
Thomas T Perls ◽  
...  
Keyword(s):  
Association Study ◽  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Genome Wide Association ◽  
Human Longevity ◽  
Mixed Effect ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
A Genome

Abstract The strong heritability of extreme human longevity supports the hypothesis that this is a genetically-regulated trait. However, association studies focused on common genetic variants have discovered a limited number of longevity-associated genes. We conducted a genome-wide association study of 4,216 individuals including 1317 centenarians from the New England Centenarian Study (median age = 104 years) using &gt;9M genetic variants imputed to the HRC panel of ~65,000 haplotypes. The set included approximately 5M uncommon variants. The associations were tested using a mixed effect logistic regression model with genotype-based kinship covariance of the random effects to adjust for cryptic relations using the package GENESIS. The analysis discovered 45 genome-wide significant SNPs (p&lt; 5E-08) including 8 new loci in chromosomes 3, 6, 7, 9, 10, 14 and 15 in addition to the APOE locus. The list includes new pQTLs in serum that suggest a new biological mechanism involved in extreme human longevity.

Genome-wide association study of plasma resistin levels identified rs1423096 and rs10401670 as possible functional variants in the Japanese population

2016 ◽  
Vol 48 (11) ◽  
pp. 874-881 ◽  
Author(s):  
Ryoichi Kawamura ◽  
Yasuharu Tabara ◽  
Akiko Tsukada ◽  
Michiya Igase ◽  
Jun Ohashi ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Association Study ◽  
Japanese Population ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Luciferase Reporter ◽  
Strong Linkage Disequilibrium ◽  
Functional Variants ◽  
Genome Wide ◽  
A Genome

Resistin is a cytokine inducing insulin resistance in mice. We previously identified single nucleotide polymorphisms (SNPs) at −420 (rs1862513) and −358 (rs3219175) located in the human resistin gene ( RETN) promoter as strong determinants for circulating resistin in the Japanese population. The objective was to identify additional functional variants for circulating resistin. We conducted a genome-wide association study in 448 Japanese subjects. A peak association signal was found on chromosome 19 where RETN is located. The top-hit SNP was SNP −358 G>A, followed by rs1423096 C>T, SNP −420 C>G, and rs10401670 C>T ( P = 5.39×10−47, 1.81×10−22, 2.09×10−16, and 9.25×10−15, respectively). Meta-analysis including another two independent general Japanese populations showed that circulating resistin was most strongly associated with SNP-358, followed by SNP-420, rs1423096, and rs10401670. Rs1423096 and rs10401670 were located in the 3′-region of RETN and were in strong linkage disequilibrium. Although these SNPs were also in linkage disequilibrium with the promoter SNPs, conditional and haplotype association analyses identified rs1423096 and rs10401670 as independent determinants for circulating resistin. Functionally, nuclear proteins specifically recognized T but not C at rs10401670 as evidenced by an electrophoretic mobility shift assay. The promoter activity of a luciferase reporter with T at either rs1423096 or rs10401670 was lower than that with C in THP-1 human monocytes. Therefore, rs1423096 and rs10401670, in addition to SNP-420 and SNP-358, were identified as possible functional variants affecting circulating resistin by the genome-wide search in the Japanese population.

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