Third, we used partitioned LD score regression46 to evaluate the enrichment of the major depression GWA findings in over 50 functional genomic annotations (Fig. 3C and Supplementary Table 8). The major finding was the significant enrichment of hSNP2 in genomic regions conserved across 29 Eutherian mammals47 (20.9 fold enrichment, P=1.4×10−15). This annotation was also the most enriched for schizophrenia46. We could not evaluate regions conserved in primates or human “accelerated” regions as there were too few for confident evaluation47. The other enrichments implied regulatory activity, and included open chromatin in human brain and an epigenetic mark of active enhancers (H3K4me1). Notably, exonic regions did not show enrichment suggesting that, as with schizophrenia17, genetic variants that change exonic sequences may not play a large role in major depression. We found no evidence that Neanderthal introgressed regions were enriched for major depression GWA findings48.
