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Chunk #19 — Online Methods — Gene-set analysis

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Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.
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Results from the GWGAS analyses were used to test for association in three types of predefined gene-sets: 7,246 curated gene-sets representing known biological and metabolic pathways were derived from 9 data resources, catalogued by and obtained from the MsigDB version 5.229 (see URLs)gene expression values from 53 tissues obtained from GTEx48, log2 transformed with pseudocount 1 after winsorization at 50 and averaged per tissuecell-type specific gene expression in 24 types of brain cells, which were calculated following the method described in Skene et al.53 and Coleman et al.37 Briefly, brain cell-type expression data was drawn from single-cell RNA sequencing data from mouse brains. For each gene, the value for each cell-type was calculated by dividing the mean Unique Molecular Identifier (UMI) counts for the given cell type by the summed mean UMI counts across all cell types. Single-cell gene-sets were derived by grouping genes into 40 equal bins by specificity of expression.