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Chunk #11 — METHODS AND MATERIALS — Statistical Analysis Methods — Pathway Analysis

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Genome-wide association study of nicotine dependence in American populations: identification of novel risk loci in both African-Americans and European-Americans.
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Meta-analyzed GWAS results from the Yale-Penn and SAGE datasets were used to identify biological pathways related to FTND. First, the number of independent SNP association tests for each gene in the genome were computed according to the method of Li and Ji (25). Next, the smallest p value for an individual SNP within each gene was multiplied by the number of independent tests in that gene to create a list of genes significantly associated with FTND after correcting for the number of tests within that gene (padj < .05). The significant genes were evaluated by pathway analysis, performed using the Ingenuity Pathway Analysis software suite (QIAGEN, Redwood City, California; http://www.ingenuity.com) to identify overrepresentation of selected genes within canonical pathways that were defined using information culled from multiple sources (Kyoto Encyclopedia of Genes and Genomes, interactome studies, manual curation, etc). Pathway analysis was done separately in AAs and EAs and a Benjamini-Hochberg false discovery rate (26) was calculated for the Fisher’s exact p value associated with each pathway.