Genomic architecture of selected schizophrenia-associated regions : co-location of non-coding and protein-coding genes

Hrovatin, Karin (author), Kunej, Tanja (author), Redenšek Trampuž, Sara (author), Terzić, Tea (author), Kores-Plesničar, Blanka (author), Goričar, Katja (author), Dolžan, Vita (author)

Background: Non-coding RNAs (ncRNAs) are increasingly recognized as important factors in the progression of schizophrenia (SZ); however, their involvement in disease etiology remains incompletely understood. This study aimed to characterize the genomic architecture of selected SZ-associated regions by examining the co-location of ncRNA and protein-coding genes and to explore sequence variants within these regions for potential associations with clinical outcomes. Methods: Genomic regions containing co-located protein-coding and ncRNA genes, specifically those with overlapping exonic sequences, were identified. Functional annotations of the selected SNPs were obtained from Ensembl, including predicted functional effects (SIFT, PolyPhen, CADD) and regulatory features. Association analyses were performed in SZ patients and controls, testing associations with disease occurrence, treatment response and psychopathological symptoms assessed by the Brief Psychiatric Rating Scale (BPRS). Results: Among 21 selected SZ-associated protein-coding genes (SZGs), seven showed genomic co-location with ncRNA genes. Exonic co-location was identified in four regions: BDNF/BDNF-AS, DDC/DDC-AS1, GNAS/GNAS-AS1 and HTR5A/HTR5A-AS1. Four SNPs within these co-located regions were selected for analysis: rs1800900 (GNAS/GNAS-AS1) and rs6265, rs11030101 and rs28722151 (BDNF/BDNF-AS). None of these associations reached statistical significance after multiple comparison adjustment. Functional annotations indicated that some variants are located in constrained elements, overlap regulatory features or have predicted deleterious effects, suggesting functional relevance. Conclusions: This exploratory study provides insights into the genomic architecture of SZ-associated regions, particularly the co-location between protein-coding SZGs and ncRNAs. It highlights the complexity of the SZ-associated genomic architecture and provides a framework for SNP prioritization and future genomic and functional studies in SZ and related disorders.

• Language: English
• Keywords: antisense lncRNA (AS-lncRNA), BDNF, non-coding RNA (ncRNA), schizophrenia, serotonin pathway, single nucleotide polymorphism, treatment response
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: BF - Biotechnical Faculty; MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: 11 str.
• Numbering: Vol. 7, issue 1, sgag025
• PID: 20.500.12556/RUL-184857
• UDC: 575:616
• ISSN on article: 2632-7899
• DOI: 10.1093/schizbullopen/sgag025
• COBISS.SI-ID: 282961667
• Publication date in RUL: 16.07.2026

Record is a part of a journal

• Title: Schizophrenia bulletin open
• Publisher: Oxford
• ISSN: 2632-7899
• COBISS.SI-ID: 51842307

Licences

• License: CC BY-NC 4.0, Creative Commons Attribution-NonCommercial 4.0 International
• Link: http://creativecommons.org/licenses/by-nc/4.0/
• Description: A creative commons license that bans commercial use, but the users don’t have to license their derivative works on the same terms.

Secondary language

• Language: Slovenian
• Keywords: genetika, genomika, nekodirajoča RNA, medicina, shizofrenija

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P1-0170
• Name: Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku