The regression coefficient τk quantifies the importance of annotation Ck, correcting for all other annotations in the model; τk will equal zero if Ck is not enriched, will be negative if belonging to Ck decreases per-SNP heritability accounting for all other annotations included, and will be positive if belonging to Ck increases per-SNP heritability, accounting for all other factors. Thus, as in our previous cell-type-specific anlaysis7, we compute P-values that test whether τk is positive. When reporting quantitative results, we normalize the coefficient τk by our estimate of the mean per-SNP heritability ∑iVar(βi)/M to make it comparable across phenotypes. The normalized coefficient can be interpreted as the proportion by which the per-SNP heritability of an average SNP would increase if τk were added to it. In addition , it is possible to estimate the total heritability, defined as ∑iVar(βi), as well as the heritability in category Ck, defined as ∑i∈CkVar(βi), by plugging estimates of τk into Equation (1), and to compare the proportion of heritability, ∑i∈CkVar(βi)/∑iVar(βi), to the proportion of SNPs, |Ck|/M, where M is the total number of SNPs7.
