PT  - JOURNAL ARTICLE
AU  - Inti Pedroso
AU  - Michael R Barnes
AU  - Anbarasu Lourdusamy
AU  - Ammar Al-Chalabi
AU  - Gerome Breen
TI  - FORGE: multivariate calculation of gene-wide p-values from Genome-Wide Association Studies
AID  - 10.1101/023648
DP  - 2015 Jan 01
TA  - bioRxiv
PG  - 023648
4099  - http://biorxiv.org/content/early/2015/07/31/023648.short
4100  - http://biorxiv.org/content/early/2015/07/31/023648.full
AB  - Genome-wide association studies (GWAS) have proven a valuable tool to explore the genetic basis of many traits. However, many GWAS lack statistical power and the commonly used single-point analysis method needs to be complemented to enhance power and interpretation. Multivariate region or gene-wide association are an alternative, allowing for identification of disease genes in a manner more robust to allelic heterogeneity. Gene-based association also facilitates systems biology analyses by generating a single p-value per gene. We have designed and implemented FORGE, a software suite which implements a range of methods for the combination of p-values for the individual genetic variants within a gene or genomic region. The software can be used with summary statistics (marker ids and p-values) and accepts as input the result file formats of commonly used genetic association software. When applied to a study of Crohn’s disease susceptibility, it identified all genes found by single SNP analysis and additional genes identified by large independent metaanalysis. FORGE p-values on gene-set analyses highlighted association with the Jak-STAT and cytokine signalling pathways, both previously associated with CD. We highlight the software’s main features, its future development directions and provide a comparison with alternative available software tools. FORGE can be freely accessed at https://github.com/inti/FORGE.