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Chunk #4 — RESULTS — Overview of methods

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Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types.
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weakly specifically expressed (i.e. higher average expression in the focal tissue). For a few of the data sets analyzed, we modified our approach to constructing the set of specifically expressed genes to better take advantage of the data available (Online Methods). We add 100kb windows on either side of the transcribed region of each gene in the set of specifically expressed genes to construct a genome annotation corresponding to the focal tissue. (The choice of the parameters 10% and 100kb is discussed in the Supplementary Note; our results are robust to these choices (see below).) Finally, we apply stratified LD score regression7 to GWAS summary statistics to evaluate the contribution of the focal genome annotation to trait heritability (Online Methods). We jointly model the annotation corresponding to the focal tissue, a genome annotation corresponding to all genes, and the 52 annotations in the “baseline model”7 (including genic regions, enhancer regions, and conserved regions; see Table S1). A positive regression coefficient for the focal annotation in this regression represents a positive contribution of this annotation to trait heritability, conditional on the other annotations. We report regression coefficients, normalized by mean per-SNP heritability, together with a P-value to test whether the regression