Recently, genetic and molecular evidence has implicated myeloid cells in the etiology of AD, including our finding that AD risk alleles are enriched for cis-eQTL effects in monocytes but not CD4+ T-lymphocytes21. To extend this finding and identify relevant cell types in AD, we used stratified LD score regression to estimate enrichment of AD heritability (measured by summary statistics from IGAP GWAS1) partitioned by 220 cell type–specific functional annotations as described by Finucane et al.25. We found a significant enrichment of AD heritability in hematopoietic cells of the myeloid and B-lymphoid lineage (e.g., 14.49 fold enrichment, P=3.49×10−5 in monocytes/CD14 enhancers/H3K4me1 and 12.33 fold enrichment, P=1.41×10−6 in B-cells/CD19 enhancers/H3K4me1). In contrast schizophrenia (SCZ) heritability was not enriched in hematopoietic cells (1.24 fold enrichment, P=0.53, as measured by summary statistics from the Psychiatric Genomics Consortium [PGC] GWAS26) but was significantly enriched in brain (18.61 fold enrichment, P=1.38×10−4 in fetal brain promoters/H3K4me3, Supplementary Table 6). These results suggest that myeloid cells specifically modulate AD susceptibility.
