A resource of induced pluripotent stem cell (iPSC) lines including clinical, genomic, and cellular data from genetically isolated families with mood and psychotic disorders
Year: 2023
Type: article
Abstract: Genome-wide (GWAS) and copy number variant (CNV) association studies have reproducibly identified numerous risk alleles associated with bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ), but biological characterization of these alleles lags gene discovery, owing to the inaccessibility of live human brain cells and inadequate animal models for human psychiatric conditions. Human-derived induced pluripotent stem cells (iPSCs) provide a renewable cellular reagent that can be differentiated into living, disease-relevant cells and 3D brain organoids carrying the full complement of genetic variants present in the donor germline. Experimental studies of iPSC-derived cells allow functional characterization of risk alleles, establishment of causal relationships between genes and neurobiology, and screening for novel therapeutics. Here we report the creation and availability of an iPSC resource comprising clinical, genomic, and cellular data obtained from genetically isolated families with BD and related conditions. Results from the first 324 study participants, 61 of whom have validated pluripotent clones, show enrichment of rare single nucleotide variants and CNVs overlapping many known risk genes and pathogenic CNVs. This growing iPSC resource is available to scientists pursuing functional genomic studies of BD and related conditions.
Source: Translational Psychiatry
Authors: Sevilla D. Detera-Wadleigh, Layla Kassem, Emily Besancon, Fabiana Lopes, Nirmala Akula, Heejong Sung, Meghan Blattner, Laura Sheridan, Ley Nadine Lacbawan, Joshua Garcia, Francis Gordovez, Katherine Hosey, Cassandra Donner, Claudio Salvini, Thomas Schulze, David T. W. Chen, Bryce England, Joanna Cross, Xueying Jiang, Winston Corona, Jill Russ, Barbara Mallon, Amalia Dutra, Evgenia Pak, Joe Steiner, Nasir Malik, Theresa de Guzman, Natia Horato, Mariana B. Mallmann, Victoria Mendes, Amanda L. Dűck, Antonio E. Nardi, Francis J. McMahon
Institutions: National Institutes of Health, National Institute of Mental Health, Universidade Federal do Rio de Janeiro, Brown University, Johns Hopkins University, Upstate University Hospital, Institut für Psychiatrische Phänomik und Genomik, Ludwig-Maximilians-Universität München, Center for Scientific Review, National Human Genome Research Institute, National Institute of Neurological Disorders and Stroke
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,790
Funders: U.S. Department of Health and Human Services, Regeneron Pharmaceuticals, University of Exeter, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Human Genome Research Institute, National Institute of Neurological Disorders and Stroke
OpenAlex ID: W4389848809