Metabolomics Network Analysis of Various Genotypes Associated with Schizophrenia Gene Variant.

Background: This study investigates metabolic perturbations in serum samples associated with different genotypes (AA, AC, and CC) of the schizophrenia susceptibility gene NOS1AP-rs12742393.

Methods: Publicly available datasets acquired using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS) were analyzed by employing network and enrichment approaches.

Results: Key metabolites, including tryptophan, 2-aminobutyric acid, palmitic acid, and 5-hydroxytryptophan, were strongly linked to metabolic networks in genotypes AA-AC and AA. Enrichment analysis was conducted to identify metabolite sets differentially distributed across these genotypes, with a particular focus on genotype AA.

Conclusions: The findings suggest that NOS1AP-rs12742393 contributes to complex metabolic alterations involving amino acids, organic compounds, fatty acids, and cholic acids. Moreover, serum metabolome analysis demonstrates sufficient sensitivity and specificity to provide insights into NOS1AP-rs12742393 genotype-associated metabolic profiles, supporting a network-based approach to understanding schizophrenia susceptibility.