Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent <i>NRXN1</i> and <i>ABCB11</i> disruptions.

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 transport

SUBMITTER: Maury EA 

PROVIDER: S-EPMC10435376 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature