Genomic Architecture of Selected Schizophrenia-Associated Regions: Co-location of Non-coding and Protein-Coding Genes

Area of Science:

• Genomics
• Neuroscience
• Molecular Biology

Background:

• Non-coding RNAs (ncRNAs) are increasingly implicated in schizophrenia (SZ) progression.
• The precise role of ncRNAs in SZ disease etiology remains unclear.
• Understanding the genomic architecture of SZ-associated regions is crucial.

Purpose of the Study:

• To characterize the genomic architecture of SZ-associated regions.
• To examine the co-location of ncRNA and protein-coding genes in SZ.
• To explore sequence variants for associations with clinical outcomes in SZ.

Main Methods:

• Identified genomic regions with co-located protein-coding and ncRNA genes, including overlapping exonic sequences.
• Obtained functional annotations for single nucleotide polymorphisms (SNPs) from Ensembl, assessing predicted functional effects and regulatory features.
• Performed association analyses in SZ patients and controls for disease occurrence, treatment response, and psychopathological symptoms.

Main Results:

• Seven of 21 selected SZ-associated protein-coding genes (SZGs) showed genomic co-location with ncRNA genes.
• Exonic co-location was observed in four regions: BDNF/BDNF-AS, DDC/DDC-AS1, GNAS/GNAS-AS1, and HTR5A/HTR5A-AS1.
• No statistically significant associations were found for four selected SNPs (rs1800900, rs6265, rs11030101, rs28722151) after multiple comparison adjustment; however, two variants showed potential functional relevance.

Conclusions:

• This study offers insights into the genomic architecture of SZ-associated regions, particularly the interplay between protein-coding SZGs and ncRNAs.
• The findings highlight the complexity of SZ-associated genomic architecture.
• A framework is provided for SNP prioritization and future genomic/functional studies in SZ and related disorders.