Cell-type specific H-MAGMA further recapitulated cellular expression profiles of disease risk genes. For example, we observed excitatory neuronal expression of psychiatric disorder risk genes, microglial expression of AD- and MS-associated genes, and astrocytic expression of PD- and ALS-associated genes (Fig. 3a). As astrocytes gain inflammatory profiles with aging38, we further assessed age-associated astrocytic expression of degenerative disorder risk genes derived from astrocytic H-MAGMA. We found that AD- and PD-associated genes were expressed in mature astrocytes, while ALS-associated genes were highly expressed in fetal astrocytes. MS-associated genes were highly expressed in glioblastoma, consistent with the emerging view that astrocyte-mediated neuroinflammation is a key contributor to the MS pathogenesis39. Further, psychiatric disorder-associated genes showed prenatal enrichment with a peak during mid-gestation, while degenerative disorder-associated genes were postnatally enriched with a gradual increase in expression across a lifespan (Fig. 3b–c). One remarkable difference between cell-type specific and brain homogenate H-MAGMA was postnatal expression of MS-associated genes from astrocytic H-MAGMA, which was not detected in brain homogenate.
