A core collection of pan-schizophrenia genes allows building cohort-specific signatures of affected brain

Sci Rep. 2019 Sep 3;9(1):12671. doi: 10.1038/s41598-019-48605-3.

Abstract

To investigate whether pan-schizophrenia genes could be leveraged for building cohort-specific signatures reflecting the functioning of the affected brain, we first collected 1,518 schizophrenia-related genes upon analysis of 12,316 independent peer-reviewed literature sources. More than half of these genes have been reported in at least 3 independent studies, and a majority (81.4%) were enriched within 156 functional pathways (p-values < 1e-15). Gene expression profiles of brain tissues were extracted from 14 publicly available independent datasets, and classified into "schizophrenia" and "normal" bins using dataset-specific subsets of core schizophrenia collection genes built with either a sparse representation-based variable selection (SRVS) approach or with analysis of variance (ANOVA)-based gene selection approach. Results showed that cohort-specific classifiers by both SRVS and ANOVA methods are capable of providing significantly higher accuracy in the diagnosis of schizophrenia than using the whole core genes (p < 3.38e-6), with relatively low sensitivity to the ethnic backgrounds or areas of brain biopsies. Our results suggest that the formation of consensus collection of pan-schizophrenia genes and its dissection into the functional components could be a feasible alternative to the expansion of sample size, which is needed for further in-depth studies of the pathophysiology of the human brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Brain / metabolism*
  • Brain / pathology
  • Cohort Studies
  • Databases, Genetic
  • Female
  • Gene Expression Regulation
  • Humans
  • Male
  • Schizophrenia / genetics
  • Schizophrenia / pathology*
  • Signal Transduction / genetics