Single-cell genomics and regulatory networks for 388 human brains

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into a resource comprising >2.8 million nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550,000 cell type-specific regulatory elements and >1.4 million single-cell expression quantitative trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest…

• NS
  National Science Foundation

  Award: 2144475
• UD
  U.S. Department of Veterans Affairs

  Awards: VISN1, BX002395
• AF
  American Foundation for Suicide Prevention
• YU
  Yale University
• WC
  Waisman Center

  Award: P50HD105353
• NA
  National Alliance for Research on Schizophrenia and Depression
• NI
  National Institutes of Health

  Awards: R01MH125516, R01MH110921, R01MH109715, R01MH110927, U01MH116492, R01MH126459, MH109897, U01MH116442, R01HG012572, R01MH105898, R01NS128523, R01MH121521, R21NS128761, U01MH103340, U01MH114812, R01MH109677, RF1MH128695, R01MH110920, R21MH105853, U01MH122591, U01MH122849, U01MH116441, U01MH103392, U01MH116489, R01MH117406, P50HD105353, R21NS127432, R01AG067025
• NI
  National Institute of Mental Health

  Awards: R21MH105853, U01MH103392, R01MH126393, R01MH117293, U01MH116487, R56MH114901, RF1-MH128970, RF1MH128695, U01MH116492, R21MH103877, R01MH110927, U01MH103339, R01MH125516, U01MH122849, R01MH117406, 5U01MH116489, U01MH116441, U01MH116438, U01MH114812, R01MH111721, R21MH109956, R01MH105898, R01MH126459, R01MH094714, R01-MH109897, U01MH116442, R01MH109677, R01MH121521, R01-MH125246, U01MH122591, R01-MH123922, MH109897, R01MH117292, R01MH110921, U01MH122509