title: JAG: A Computational Tool to Evaluate the Role of Gene-Sets in Complex Traits.
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.
authors.affiliation: Department of Complex Trait Genetics, Neuroscience Campus Amsterdam, VU University & VU Medical Center, Amsterdam 1081HV, The Netherlands. e.s.lips@vu.nl.
authors.forename: Esther S
authors.initials: ES
authors.lastname: Lips
authors.affiliation: Netherlands Bioinformatics Centre, Geert de Grooteplein 28, Nijmegen 6525 GA, The Netherlands. kooyman@gmail.com.|Delft Bioinformatics Lab, Delft University of Technology, Delft 2600GA, The Netherlands. kooyman@gmail.com.
authors.forename: Maarten
authors.initials: M
authors.lastname: Kooyman
authors.affiliation: Department of Complex Trait Genetics, Neuroscience Campus Amsterdam, VU University & VU Medical Center, Amsterdam 1081HV, The Netherlands. c.deleeuw@science.ru.nl.|Radboud University Nijmegen, Nijmegen 6525EC, The Netherlands. c.deleeuw@science.ru.nl.
authors.forename: Christiaan
authors.initials: C
authors.lastname: de Leeuw
authors.affiliation: Department of Complex Trait Genetics, Neuroscience Campus Amsterdam, VU University & VU Medical Center, Amsterdam 1081HV, The Netherlands. d.posthuma@vu.nl.
authors.forename: Danielle
authors.initials: D
authors.lastname: Posthuma
keywords: GWAS; biological pathway; gene-set analysis; genetic association; pathway analysis