Associations between prefrontal PI (16:0/20:4) lipid, TNC mRNA, and APOA1 protein in schizophrenia: A trans-omics analysis in post-mortem brain

Abstract

BackgroundThough various mechanisms have been proposed for the pathophysiology of schizophrenia, the full extent of these mechanisms remains unclear, and little is known about the relationships among them. We carried out trans-omics analyses by comparing the results of the previously reported lipidomics, transcriptomics, and proteomics analyses; all of these studies used common post-mortem brain samples.MethodsWe collected the data from three aforementioned omics studies on 6 common post-mortem samples (3 schizophrenia patients and 3 controls), and analyzed them as a whole group sample. Three correlation analyses were performed for each of the two of three omics studies in these samples. In order to discuss the strength of the correlations in a limited sample size, the p-values of each correlation coefficient were confirmed using the Student’s t-test. In addition, partial correlation analysis was also performed for some correlations, to verify the strength of the impact of each factor on the correlations.ResultsThe following three factors were strongly correlated with each other: the lipid level of phosphatidylinositol (PI) (16:0/20:4), the amount of TNC mRNA, and the quantitative signal intensity of APOA1 protein. PI (16:0/20:4) and TNC showed a positive correlation, while PI (16:0/20:4) and APOA1, and TNC and APOA1 showed negative correlations. All of these correlations reached at p < 0.01. PI (16:0/20:4) and TNC were decreased in the prefrontal cortex of schizophrenia samples, while APOA1 was increased. Partial correlation analyses among them suggested that PI (16:0/20:4) and TNC have no direct correlation, but their relationships are mediated by APOA1.ConclusionThe current results suggest that these three factors may provide new clues to elucidate the relationships among the candidate mechanisms of schizophrenia, and support the potential of trans-omics analyses as a new analytical method.