Consensus molecular environment of schizophrenia risk genes in coexpression networks shifting across age and brain regions.

Autor: Pergola G; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.; Group of Psychiatric Neuroscience, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Parihar M; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA., Sportelli L; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.; Group of Psychiatric Neuroscience, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy., Bharadwaj R; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA., Borcuk C; Group of Psychiatric Neuroscience, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy., Radulescu E; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA., Bellantuono L; Group of Psychiatric Neuroscience, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.; Istituto Nazionale di Fisica Nucleare, Bari, Italy., Blasi G; Group of Psychiatric Neuroscience, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.; Azienda Ospedaliero Universitaria Consorziale Policlinico, Bari, Italy., Chen Q; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA., Kleinman JE; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Wang Y; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA., Sripathy SR; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA., Maher BJ; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Monaco A; Istituto Nazionale di Fisica Nucleare, Bari, Italy.; Dipartimento Interateneo di Fisica, Università degli Studi di Bari Aldo Moro, Bari, Italy., Rossi F; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.; Group of Psychiatric Neuroscience, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy., Shin JH; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA., Hyde TM; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Bertolino A; Group of Psychiatric Neuroscience, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.; Azienda Ospedaliero Universitaria Consorziale Policlinico, Bari, Italy., Weinberger DR; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2023 Apr 14; Vol. 9 (15), pp. eade2812. Date of Electronic Publication: 2023 Apr 14.
DOI: 10.1126/sciadv.ade2812
Abstrakt: Schizophrenia is a neurodevelopmental brain disorder whose genetic risk is associated with shifting clinical phenomena across the life span. We investigated the convergence of putative schizophrenia risk genes in brain coexpression networks in postmortem human prefrontal cortex (DLPFC), hippocampus, caudate nucleus, and dentate gyrus granule cells, parsed by specific age periods (total N  = 833). The results support an early prefrontal involvement in the biology underlying schizophrenia and reveal a dynamic interplay of regions in which age parsing explains more variance in schizophrenia risk compared to lumping all age periods together. Across multiple data sources and publications, we identify 28 genes that are the most consistently found partners in modules enriched for schizophrenia risk genes in DLPFC; twenty-three are previously unidentified associations with schizophrenia. In iPSC-derived neurons, the relationship of these genes with schizophrenia risk genes is maintained. The genetic architecture of schizophrenia is embedded in shifting coexpression patterns across brain regions and time, potentially underwriting its shifting clinical presentation.
Databáze: MEDLINE