Details

Autor(en) / Beteiligte

• Maury, Eduardo A
• Sherman, Maxwell A
• Genovese, Giulio
• Gilgenast, Thomas G
• Kamath, Tushar
• Burris, S J
• Rajarajan, Prashanth
• Flaherty, Erin
• Akbarian, Schahram
• Chess, Andrew
• McCarroll, Steven A
• Loh, Po-Ru
• Phillips-Cremins, Jennifer E
• Brennand, Kristen J
• Macosko, Evan Z
• Walters, James T R
• O'Donovan, Michael
• Sullivan, Patrick
• Sebat, Jonathan
• Lee, Eunjung A
• Walsh, Christopher A

Titel

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

Ist Teil von

• Cell genomics, 2023-08, Vol.3 (8), p.100356-100356, Article 100356

Ort / Verlag

United States: Elsevier

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.