[Search for risk genes in schizophrenia]

Abstract

Background: Schizophrenia is a severe psychiatric disease affecting approximately 0.5-1% of the general population. The relative contribution of genetic factors has been estimated to be 64-81%.

Objective: This review summarizes recent efforts to identify genetic variants associated with schizophrenia.

Methods: Relevant linkage and candidate genes as well as genome wide association studies, studies on copy number variants and next generation sequencing are presented and discussed.

Results: The latest and worldwide largest study on the genetics of schizophrenia found 128 genome wide significant single nucleotide polymorphisms (SNP) and 108 genome wide loci. The most obvious association is with genetic variations in the major histocompatibility complex (MHC). Besides polymorphisms, structural variants in the form of copy number variants (CNV), such as microdeletions and microduplications have a very high impact in a subgroup of patients. These CNVs are mainly microdeletions on 1q21.1, 2p16.3, 3q29, 15q13.3 and 16p11.2 as well as a large deletion on 22q11.21 and a microduplication on 16p11.2.

Conclusion: A large new body of evidence on the genetics of schizophrenia is expected through next generation sequencing approaches. Future studies will particularly address the functional characterization of genetic variants.

Keywords: Copy number variant (CNV); Genetics; Genome wide association study (GWAS); Major histocompatibility complex (MHC); Next generation sequencing (NGS).