Systematic review of the Genomewide Association Studies (GWAS) in schizophrenia

Introduction: Heritability in schizophrenia can reach up to 80% and the risk in families is 5-10 times higher than in the general population. The large contribution of genetics in this disorder has led to a growing interest in its study. Objectives: To review the findings of genetic studies known as Genomewide Association Studies (GWAS) on schizophrenia. Method: Systematic search using Pubmed with the key words GWAS and (psychosis) or (schizophrenia). The following web pages have been reviewed: http://www.szgene.org/largescale.asp and www.genome.gov/gwastudies/. Results: The GWAS have focused on causal biological aspects, such as the histocompatibility complex, glutamate metabolism, apoptosis and inflammatory processes, and the immune system (TNF-beta, TNFR1). Also focused in the search were the genes that modulate the appearance of secondary metabolic and cardiac effects and secondary effects in subjects with schizophrenia and on anti-psychotic treatment. In neurorecognition, over-expression of the MET proto-oncogene (MET) has been associated with a low susceptibility for schizophrenia and a better cognitive performance, as well as a lower susceptibility for the incidence of cancer. Mention is also made of the different genes that mediate in cognitive functioning depending on the anti-psychotic treatment received. Conclusions: The main interests of the GWAS during the last few years have been the neurobiological pathways involved in schizophrenia. The discoveries arising from these studies have been limited. This has led to an innovative approach on the aetiological study of the disorder by studying gene-environment interactions. (C) 2011 SEP y SEPB. Published by Elsevier Espana, S.L. All rights reserved.