Abstract
BackgroundWhile genome-wide association studies identified some promising candidates for schizophrenia, the majority of risk genes remained unknown. We were interested in testing whether integration gene expression and other functional information could facilitate the identification of susceptibility genes and related biological pathways.ResultsWe conducted high throughput sequencing analyses to evaluate mRNA expression in blood samples isolated from 3 schizophrenia patients and 3 healthy controls. We also conducted pooled sequencing of 10 schizophrenic patients and matched controls. Differentially expressed genes were identified by t-test. In the individually sequenced dataset, we identified 198 genes differentially expressed between cases and controls, of them 19 had been verified by the pooled sequencing dataset and 21 reached nominal significance in gene-based association analyses of a genome wide association dataset. Pathway analysis of these differentially expressed genes revealed that they were highly enriched in the immune related pathways. Two genes, S100A8 and TYROBP, had consistent changes in expression in both individual and pooled sequencing datasets and were nominally significant in gene-based association analysis.ConclusionsIntegration of gene expression and pathway analyses with genome-wide association may be an efficient approach to identify risk genes for schizophrenia.
Highlights
While genome-wide association studies identified some promising candidates for schizophrenia, the majority of risk genes remained unknown
Except the findings from rare copy number variations [10,11,12,13], the effects of individual genes overall are modest or weak. These results suggest that many genes with moderate or small effects may be involved in schizophrenia [14]
We further examined the association of the discovered differentially expressed genes (DEGs) using genome-wide association (GWA) data from the molecular genetics of schizophrenia (MGS) study
Summary
While genome-wide association studies identified some promising candidates for schizophrenia, the majority of risk genes remained unknown. Recent genetic studies, including genome-wide association (GWA) studies, have identified several promising candidate genes and loci. One of the most consistent findings in GWA studies is the major histocompatibility (MHC) region in 6p [1,2,3] This finding strongly implicates the immune system as being involved in the development of schizophrenia. Except the findings from rare copy number variations [10,11,12,13], the effects of individual genes overall are modest or weak These results suggest that many genes with moderate or small effects may be involved in schizophrenia [14]. Integration of other functional studies or utilization of high throughput technologies may increase the power to detect other schizophrenia candidate genes
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