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Publicly available hiPSC lines with extreme polygenic risk scores for modeling schizophrenia

By Kristina Dobrindt, Hanwen Zhang, Debamitra Das, Sara Abdollahi, Tim Prorok, Sulagna Ghosh, Sarah Weintraub, Giulio Genovese, Samuel K Powell, Anina Lund, Schahram Akbarian, Kevin Eggan, Steven McCarroll, Jubao Duan, Dimitrios G. Avramopoulos, Kristen J. Brennand

Posted 04 Jul 2020
bioRxiv DOI: 10.1101/2020.07.04.185348

Schizophrenia (SZ) is a common and debilitating psychiatric disorder with limited effective treatment options. Although highly heritable, risk for this polygenic disorder depends on the complex interplay of hundreds of common and rare variants. Translating the growing list of genetic loci significantly associated with disease into medically actionable information remains an important challenge. Thus, establishing platforms with which to validate the impact of risk variants in cell-type-specific and donor-dependent contexts is critical. Towards this, we selected and characterize a collection of twelve human induced pluripotent stem cell (hiPSC) lines derived from control donors with extremely low and high SZ polygenic risk scores (PRS). These hiPSC lines are publicly available at the California Institute for Regenerative Medicine (CIRM). The suitability of these extreme PRS hiPSCs for CRISPR-based isogenic comparisons of neurons and glia was evaluated across three independent laboratories, identifying 9 out of 12 meeting our criteria. We report a standardized resource of publicly available hiPSCs, with which we collectively commit to conducting future CRISPR-engineering, in order to facilitate comparison and integration of functional validation studies across the field of psychiatric genetics. ### Competing Interest Statement The authors have declared no competing interest.

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