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Chunk #58 — Online Methods — Gene and gene-set analyses

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Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.
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A gene-set analysis was then performed on our gene-based results using gene annotation files from the Gene Ontology Consortium (http://geneontology.org/) 82 and the Molecular Signatures Database v5.2 83. The annotation file includes gene-sets covering three ontologies; molecular function, cellular components, and biological function and consisted of 5,917 gene-sets. To correct for multiple testing, we used the MAGMA default setting of 10,000 permutations, and applied a Bonferroni correction (α = 0.05 / 5,917; P < 8.45 × 10-6). Additional gene-sets were obtained from Skene, et al. 15 providing expression-weighted enrichment for seven brain cell-types (astrocytes ependymal, endothelial mural, interneurons, microglia, oligodendrocytes, somatosensory pyramidal neurons, and hippocampus CA1 pyramidal neurons). These brain cell-types were assessed in MAGMA using the default setting of 10,000 permutations with a Bonferroni correction (α = 0.05 / 7; P < 7.14 × 10-3) used to assess significance.