In addition to the analyses using the full baseline model, we performed analyses using cell-type-specific annotations from the four histone marks H3K4me1, H3K4me3, H3K9ac, and H3K27ac. Each cell-type-specific annotation corresponds to a histone mark in a single cell type—for example, H3K27ac in liver cells—and there are 220 such annotations in total (Supplementary Table 2, Online Methods). When ranking these 220 cell-type-specific annotations, we want to control for overlap with the functional categories in the full baseline model, but not for overlap with the 219 other cell-type-specific annotations. Thus, we add these annotations individually to the baseline model, creating 220 separate models, each with 54 annotations. Then for a given phenotype, we run LD score regression once each on the 220 models and rank the cell-type-specific annotations by the P-value of the coefficient τC of the annotation in the corresponding analysis. This P-value tests whether the annotation contributes significantly to per-SNP heritability after controlling for the effects of the annotations in the full baseline model.
