Our method for partitioning heritability from summary statistics, called stratified LD score regression, relies on the fact that the χ2 association statistic for a given SNP includes the effects of all SNPs that it tags [15,16]. Thus, for a polygenic trait, SNPs with high LD score will have higher χ2 statistics on average than SNPs with low LD score [16]. This might be driven either by the higher likelihood of these SNPs to tag an individual large effect, or their ability to tag multiple weak effects. If we partition SNPs into functional categories with different contributions to heritability, then LD to a category that is enriched for heritability will increase the χ2 statistic of a SNP more than LD to a category that does not contribute to heritability. Thus, our method determines that a category of SNPs is enriched for heritability if SNPs with high LD to that category have higher χ2 statistics than SNPs with low LD to that category.
