Schizophrenia-associated Somatic Copy-number Variants from 12,834 Cases Reveal Recurrent and Disruptions

Overview

Journal Cell Genom

Date 2023 Aug 21

PMID 37601975

Authors

Eduardo A Maury

Maxwell A Sherman

Giulio Genovese

Thomas G Gilgenast

Tushar Kamath

S J Burris

Prashanth Rajarajan

Erin Flaherty

Schahram Akbarian

Andrew Chess

Steven A McCarroll

Po-Ru Loh

Jennifer E Phillips-Cremins

Kristen J Brennand

Evan Z Macosko

James T R Walters

Michael ODonovan

Patrick Sullivan

Jonathan Sebat

Eunjung A Lee

Christopher A Walsh

Affiliations

Soon will be listed here.

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 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding -regulatory elements upon 5' deletions in . We also observed recurrent intragenic deletions of , encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk.

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