LDSC was also used to partition hSNP2 by genomic features24,46. We tested for enrichment of hSNP2 based on genomic annotations partitioning hSNP2 proportional to bp length represented by each annotation. We used the “baseline model” which consists of 53 functional categories. The categories are fully described elsewhere46, and included conserved regions47, USCC gene models (exons, introns, promoters, UTRs), and functional genomic annotations constructed using data from ENCODE 87 and the Roadmap Epigenomics Consortium88. We complemented these annotations by adding introgressed regions from the Neanderthal genome in European populations89 and open chromatin regions from the brain dorsolateral prefrontal cortex. The open chromatin regions were obtained from an ATAC-seq experiment performed in 288 samples (N=135 controls, N=137 schizophrenia, N=10 bipolar, and N=6 affective disorder)90. Peaks called with MACS91 (1% FDR) were retained if their coordinates overlapped in at least two samples. The peaks were re-centered and set to a fixed width of 300bp using the diffbind R package92. To prevent upward bias in heritability enrichment estimation, we added two categories created by expanding both the Neanderthal introgressed regions and open chromatin regions by 250bp on each side.
