Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

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• dc.contributor.author Maury, Eduardo A.
• dc.contributor.author Brain Somatic Mosaicism Network
• dc.contributor.author Walsh, Christopher A.
• dc.date.accessioned 2023-11-30T07:32:42Z
• dc.date.available 2023-11-30T07:32:42Z
• dc.date.issued 2023
• dc.description.abstract While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)-present in some but not all cells-remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e-4), with recurrent somatic deletions of exons 1-5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5' deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk.
• dc.format.mimetype application/pdf
• dc.identifier.citation Maury EA, Sherman MA, Genovese G, Gilgenast TG, Kamath T, Burris SJ, et al. Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions. Cell Genom. 2023 Jul 6;3(8):100356. DOI: 10.1016/j.xgen.2023.100356
• dc.identifier.doi http://dx.doi.org/10.1016/j.xgen.2023.100356
• dc.identifier.issn 2666-979X
• dc.identifier.uri http://hdl.handle.net/10230/58413
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Cell Genom. 2023 Jul 6;3(8):100356
• dc.rights © 2023 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword ABCB11
• dc.subject.keyword NRXN1
• dc.subject.keyword Genomics
• dc.subject.keyword Mosaicism
• dc.subject.keyword Schizophrenia
• dc.subject.keyword Somatic
• dc.subject.keyword Structural variants
• dc.subject.keyword Treatment resistance
• dc.title Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion