3.10 Augmenting
GWAS Signals with
araGWAB
SNPs that fail to pass the significance threshold corrected for multiple hypotheses can be a false-negative and still be associated with
the phenotype. Genes involved with the same phenotype tend to be
functionally associated. Therefore, the limited statistical power of
GWAS can be augmented by functional links to other genes that are
likely to be associated with the phenotype. We previously developed
a web application for network-based augmentation of GWAS in
Arabidopsis, araGWAB (Arabidopsis genome-wide association
boosting) [13], which is summarized in Fig. 5. The whole procedure of GWAS boosting using araGWAB web application can be
conducted as follows.
Fig. 5 Overview of network-based augmentation of GWAS signals using araGWAB. (a) araGWAB uses the
original GWAS results as input data. Only a few SNPs (e.g., SNP-1, SNP-2, and SNP-3 in the example) pass the
significance threshold (dotted line) by GWAS alone, but many other SNPs such as SNP-4 still show high
significance in the sub-threshold region. (b) araGWAB assigns p-values of SNP with highest significance in the
same LD block. In this example, gene A, gene B, gene C, and gene D will have p-values of SNP-1, SNP-2,
SNP-3, and SNP-4, respectively. (c) Genes associated with the same phenotype are often linked in the
functional network as shown in the connected subnetwork of the four genes. (d) In the network, each gene
receives significant propagated scores from the connected genes that are associated with the phenotype. In
the example, gene D had relatively low significance by GWAS alone, but increased in significance with addition
of propagated significance from connected phenotype-associated genes with edge weight. Consequently,
gene D, which was an insignificant candidate by GWAS alone, became a significant candidate for the
phenotype after network-based augmentation of original GWAS signals
Genome-Wide Association Studies in Arabidopsis
203
GWAS Signals with
araGWAB
SNPs that fail to pass the significance threshold corrected for multiple hypotheses can be a false-negative and still be associated with
the phenotype. Genes involved with the same phenotype tend to be
functionally associated. Therefore, the limited statistical power of
GWAS can be augmented by functional links to other genes that are
likely to be associated with the phenotype. We previously developed
a web application for network-based augmentation of GWAS in
Arabidopsis, araGWAB (Arabidopsis genome-wide association
boosting) [13], which is summarized in Fig. 5. The whole procedure of GWAS boosting using araGWAB web application can be
conducted as follows.
Fig. 5 Overview of network-based augmentation of GWAS signals using araGWAB. (a) araGWAB uses the
original GWAS results as input data. Only a few SNPs (e.g., SNP-1, SNP-2, and SNP-3 in the example) pass the
significance threshold (dotted line) by GWAS alone, but many other SNPs such as SNP-4 still show high
significance in the sub-threshold region. (b) araGWAB assigns p-values of SNP with highest significance in the
same LD block. In this example, gene A, gene B, gene C, and gene D will have p-values of SNP-1, SNP-2,
SNP-3, and SNP-4, respectively. (c) Genes associated with the same phenotype are often linked in the
functional network as shown in the connected subnetwork of the four genes. (d) In the network, each gene
receives significant propagated scores from the connected genes that are associated with the phenotype. In
the example, gene D had relatively low significance by GWAS alone, but increased in significance with addition
of propagated significance from connected phenotype-associated genes with edge weight. Consequently,
gene D, which was an insignificant candidate by GWAS alone, became a significant candidate for the
phenotype after network-based augmentation of original GWAS signals
Genome-Wide Association Studies in Arabidopsis
203