S0,c is a matrix containing estimates of genetic covariance in annotation c, without controlling for overlap with other annotations. The elements ζc composing S0,c can be derived from the τc estimates from the multivariate S-LDSC model in combination with knowledge of annotation overlap. Thus, the zero-order contribution of target annotation t to heritability or co-heritability is written as: ζt=∑c(∣Cc∩Ct∣∣Cc∣)τc where ∣Cc ∩ Ct∣ is the number of SNPs in annotation c that are also in target annotation t, and ∣Cc∣ is the total number of SNPs in annotation c (alternatively expressed as Mc), such that (∣Cc∩Ct∣∣Cc∣) reflects the proportion of SNPs in annotatio c that are also in target annotation t. This proportion is used to weight the term τc for each annotation in deriving the zero-order contribution of target annotation t to heritability or coheritability.
