Transcriptional signatures of schizophrenia in hiPSC-derived NPCs and neurons are concordant with post-mortem adult brains

Gabriel E. Hoffman (), Brigham J. Hartley, Erin Flaherty, Ian Ladran, Peter Gochman, Douglas M. Ruderfer, Eli A. Stahl, Judith Rapoport, Pamela Sklar and Kristen J. Brennand ()
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Gabriel E. Hoffman: Icahn School of Medicine at Mount Sinai
Brigham J. Hartley: Icahn School of Medicine at Mount Sinai
Erin Flaherty: Icahn School of Medicine at Mount Sinai
Ian Ladran: Icahn School of Medicine at Mount Sinai
Peter Gochman: National Institutes of Health
Douglas M. Ruderfer: Icahn School of Medicine at Mount Sinai
Eli A. Stahl: Icahn School of Medicine at Mount Sinai
Judith Rapoport: National Institutes of Health
Pamela Sklar: Icahn School of Medicine at Mount Sinai
Kristen J. Brennand: Icahn School of Medicine at Mount Sinai

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: Abstract The power of human induced pluripotent stem cell (hiPSC)-based studies to resolve the smaller effects of common variants within the size of cohorts that can be realistically assembled remains uncertain. We identified and accounted for a variety of technical and biological sources of variation in a large case/control schizophrenia (SZ) hiPSC-derived cohort of neural progenitor cells and neurons. Reducing the stochastic effects of the differentiation process by correcting for cell type composition boosted the SZ signal and increased the concordance with post-mortem data sets. We predict a growing convergence between hiPSC and post-mortem studies as both approaches expand to larger cohort sizes. For studies of complex genetic disorders, to maximize the power of hiPSC cohorts currently feasible, in most cases and whenever possible, we recommend expanding the number of individuals even at the expense of the number of replicate hiPSC clones.

Date: 2017
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DOI: 10.1038/s41467-017-02330-5

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