Pathway-based analysis for genome-wide association studies of schizophrenia to provide new insight in schizophrenia study

Abstract

Schizophrenia (SZ) is an inheritable complex mental disease. There have been several genome-wide association studies (GWASs) of SZ to identify novel genetic susceptibility factors. To further interpret SZ GWASs, pathway-based analysis (PBA), which considers the combined effect of variants and identifies pathways associated with traits, provides a feasible solution to discover the biological function and mechanism of SZ. Furthermore, to investigate the common pathways between SZ and bipolar disorder (BD) will help explore common mechanism between psychiatric phenotypes. We performed a PBA, called improved gene set enrichment analysis (i-GSEA), on 3 independent GWASs of SZ to identify pathways associated with SZ. The results were further compared to the BD-associated pathways identified by i-GSEA for 2 BD GWASs and from literature reports. Our analysis identified a highly statistically significant association between SZ and pathway 'substrate specific channel activity' in all 3 SZ GWASs (false discovery rate (FDR) < 0.05). This association has not been reported elsewhere before. This pathway was also identified by PBA for 2 independent BD GWASs. Our results suggest that pathway 'substrate specific channel activity' is statistically significantly associated with SZ, and SZ and BD share the common biological function and mechanism represented by this pathway.

Endophenotype strategies for the study of neuropsychiatric disorders: A quest

“…Two papers [11,12] are working on the development of a battery specifically capturing neuropsychological endophenotypes for schizophrenia, and how it may help develop a research-oriented programme for studying endophenotypes for neuropsychiatric disorders. There are two papers [13,14] specifically dealing with the analysis issues including novel pathway-based analysis for genome-wide association studies for schizophrenia, and the issues we should pay attention to when applying statistics for endophenotype study. Finally, there is one paper [15] working on the establishment of a consortium for endophenotypes to study neuropsychiatric disorders in mainland China.…”