20.500.12556/RUL-184857 Genomic architecture of selected schizophrenia-associated regions co-location of non-coding and protein-coding genes 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. antisense lncRNA (AS-lncRNA) BDNF non-coding RNA (ncRNA) schizophrenia serotonin pathway single nucleotide polymorphism treatment response genetika genomika nekodirajoča RNA medicina shizofrenija true false true Angleški jezik Slovenski jezik Članek v reviji 2026-07-16 08:41:11 2026-07-16 08:41:23 2026-07-29 19:04:43 0000-00-00 00:00:00 2026 0 0 11 str. issue 1, sgag025 Vol. 7 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 575:616 2632-7899 10.1093/schizbullopen/sgag025 282961667 RAZ_Hrovatin_Karin_2026.pdf RAZ_Hrovatin_Karin_2026.pdf 1 5DC3359860541F2D0EA990FC556B8163 c459fe34d9b1010f59cc2c54136f420c53c31daa952c500f1e67063a52d94a9a e7d7aea5-858f-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=243119 https://academic.oup.com/schizbullopen/advance-article/doi/10.1093/schizbullopen/sgag025/8713272 1 2e8cdf66-80e1-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=240223 Biotehniška fakulteta Medicinska fakulteta 0 0 0