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JAG: A Computational Tool to Evaluate the Role of Gene-Sets in Complex Traits.

Lips ES, Kooyman M, de Leeuw C, Posthuma D - Genes (Basel) (2015)

Bottom Line: Gene-set analysis has been proposed as a powerful tool to deal with the highly polygenic architecture of complex traits, as well as with the small effect sizes typically found in GWAS studies for complex traits.We developed a tool, Joint Association of Genetic variants (JAG), which can be applied to Genome Wide Association (GWA) data and tests for the joint effect of all single nucleotide polymorphisms (SNPs) located in a user-specified set of genes or biological pathway.JAG is a powerful, novel tool for gene-set analysis, and can be freely downloaded from the CTG Lab website.

View Article: PubMed Central - PubMed

Affiliation: Department of Complex Trait Genetics, Neuroscience Campus Amsterdam, VU University & VU Medical Center, Amsterdam 1081HV, The Netherlands. e.s.lips@vu.nl.

ABSTRACT
Gene-set analysis has been proposed as a powerful tool to deal with the highly polygenic architecture of complex traits, as well as with the small effect sizes typically found in GWAS studies for complex traits. We developed a tool, Joint Association of Genetic variants (JAG), which can be applied to Genome Wide Association (GWA) data and tests for the joint effect of all single nucleotide polymorphisms (SNPs) located in a user-specified set of genes or biological pathway. JAG assigns SNPs to genes and incorporates self-contained and/or competitive tests for gene-set analysis. JAG uses permutation to evaluate gene-set significance, which implicitly controls for linkage disequilibrium, sample size, gene size, the number of SNPs per gene and the number of genes in the gene-set. We conducted a power analysis using the Wellcome Trust Case Control Consortium (WTCCC) Crohn's disease data set and show that JAG correctly identifies validated gene-sets for Crohn's disease and has more power than currently available tools for gene-set analysis. JAG is a powerful, novel tool for gene-set analysis, and can be freely downloaded from the CTG Lab website.

No MeSH data available.


Related in: MedlinePlus

Comparison of results from JAG’s gene-set based test results with other gene-set based tools. The −log10 transformed p-values per gene-set are plotted. Yellow dots indicate gene-sets showing significance in JAG only. Red dots indicate gene-sets with statistically significant association in the comparison tool, but not in JAG. Green dots indicate gene-sets showing significance in both tools.
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genes-06-00238-f002: Comparison of results from JAG’s gene-set based test results with other gene-set based tools. The −log10 transformed p-values per gene-set are plotted. Yellow dots indicate gene-sets showing significance in JAG only. Red dots indicate gene-sets with statistically significant association in the comparison tool, but not in JAG. Green dots indicate gene-sets showing significance in both tools.

Mentions: We also investigated the overlap in significant gene-sets detected by each method versus JAG. The results are visualized in the plots in Figure 2 (more details available in Supplementary Table S3). The p-values obtained with PLINK using JAG-like settings showed a high correlation with JAG, whereas results from the other methods were less correlated with JAG, which partly reflects different underlying hypotheses of these methods.


JAG: A Computational Tool to Evaluate the Role of Gene-Sets in Complex Traits.

Lips ES, Kooyman M, de Leeuw C, Posthuma D - Genes (Basel) (2015)

Comparison of results from JAG’s gene-set based test results with other gene-set based tools. The −log10 transformed p-values per gene-set are plotted. Yellow dots indicate gene-sets showing significance in JAG only. Red dots indicate gene-sets with statistically significant association in the comparison tool, but not in JAG. Green dots indicate gene-sets showing significance in both tools.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488663&req=5

genes-06-00238-f002: Comparison of results from JAG’s gene-set based test results with other gene-set based tools. The −log10 transformed p-values per gene-set are plotted. Yellow dots indicate gene-sets showing significance in JAG only. Red dots indicate gene-sets with statistically significant association in the comparison tool, but not in JAG. Green dots indicate gene-sets showing significance in both tools.
Mentions: We also investigated the overlap in significant gene-sets detected by each method versus JAG. The results are visualized in the plots in Figure 2 (more details available in Supplementary Table S3). The p-values obtained with PLINK using JAG-like settings showed a high correlation with JAG, whereas results from the other methods were less correlated with JAG, which partly reflects different underlying hypotheses of these methods.

Bottom Line: Gene-set analysis has been proposed as a powerful tool to deal with the highly polygenic architecture of complex traits, as well as with the small effect sizes typically found in GWAS studies for complex traits.We developed a tool, Joint Association of Genetic variants (JAG), which can be applied to Genome Wide Association (GWA) data and tests for the joint effect of all single nucleotide polymorphisms (SNPs) located in a user-specified set of genes or biological pathway.JAG is a powerful, novel tool for gene-set analysis, and can be freely downloaded from the CTG Lab website.

View Article: PubMed Central - PubMed

Affiliation: Department of Complex Trait Genetics, Neuroscience Campus Amsterdam, VU University & VU Medical Center, Amsterdam 1081HV, The Netherlands. e.s.lips@vu.nl.

ABSTRACT
Gene-set analysis has been proposed as a powerful tool to deal with the highly polygenic architecture of complex traits, as well as with the small effect sizes typically found in GWAS studies for complex traits. We developed a tool, Joint Association of Genetic variants (JAG), which can be applied to Genome Wide Association (GWA) data and tests for the joint effect of all single nucleotide polymorphisms (SNPs) located in a user-specified set of genes or biological pathway. JAG assigns SNPs to genes and incorporates self-contained and/or competitive tests for gene-set analysis. JAG uses permutation to evaluate gene-set significance, which implicitly controls for linkage disequilibrium, sample size, gene size, the number of SNPs per gene and the number of genes in the gene-set. We conducted a power analysis using the Wellcome Trust Case Control Consortium (WTCCC) Crohn's disease data set and show that JAG correctly identifies validated gene-sets for Crohn's disease and has more power than currently available tools for gene-set analysis. JAG is a powerful, novel tool for gene-set analysis, and can be freely downloaded from the CTG Lab website.

No MeSH data available.


Related in: MedlinePlus