To further support that PU.1 target genes expressed in myeloid cells may be associated with AD risk, we used stratified LD score regression25 to estimate enrichment of AD heritability (as measured by summary statistics from the IGAP GWAS1) partitioned on the PU.1 cistrome, as profiled by ChIP-Seq in human monocytes and macrophages35. We found a significant enrichment of AD heritability in both monocytes (47.58 fold enrichment, P=6.94×10−3) and macrophages (53.88 fold enrichment, P=1.65×10−3), but not SCZ heritability [as measured by summary statistics from the PGC GWAS26] (Supplementary Table 12). Thus, the contribution of the myeloid PU.1 target gene network to disease susceptibility is specific to AD. However, since PU.1 is a key myeloid transcription factor that regulates the expression of a large number of genes in myeloid cells, the enrichment of AD risk alleles in PU.1 binding sites could simply reflect an enrichment of AD GWAS associations for genes that are expressed in myeloid cells rather than specifically among PU.1 target genes. To attempt to address this issue, we performed stratified LD score regression of AD heritability partitioned by functional
