Partitioning the heritability estimate by cell type enrichment (Figure 2A, and Supplementary Table 6) revealed that central nervous system (CNS) and skeletal muscle tissues were enriched (Pcorrected < 0.05) for genetic variants contributing to the heritability of depression. Studies have reported altered histone modifications of skeletal muscle in response to exercise12 and suggested roles for skeletal muscle PGC-1α113 in depression. The prominence of CNS enrichment led us to examine both brain regions (Figure 2B, Figure 2C, Supplementary Figure 8, and Supplementary Table 7) and brain cell types (Supplementary Figure 9, and Supplementary Table 8). There was significant enrichment (Pcorrected < 0.05) of the anterior cingulate cortex, frontal cortex and cortex brain regions and neuron brain cells. The pseudo-coloring used in Figure 2C and Supplementary Figure 8 highlight in red the significance and effects sizes of the enriched regions of the brain associated with depression, respectively.
