May 4, 2010

Genome-wide approaches to schizophrenia

Brain Research Bulletin
Jubao DuanPablo V Gejman

Abstract

Schizophrenia (SZ) is a common and severe psychiatric disorder with both environmental and genetic risk factors, and a high heritability. After over 20 years of molecular genetics research, new molecular strategies, primarily genome-wide association studies (GWAS), have generated major tangible progress. This new data provides evidence for: (1) a number of chromosomal regions with common polymorphisms showing genome-wide association with SZ (the major histocompatibility complex, MHC, region at 6p22-p21; 18q21.2; and 2q32.1). The associated alleles present small odds ratios (the odds of a risk variant being present in cases vs. controls) and suggest causative involvement of gene regulatory mechanisms in SZ. (2) Polygenic inheritance. (3) Involvement of rare (<1%) and large (>100kb) copy number variants (CNVs). (4) A genetic overlap of SZ with autism and with bipolar disorder (BP) challenging the classical clinical classifications. Most new SZ findings (chromosomal regions and genes) have generated new biological leads. These new findings, however, still need to be translated into a better understanding of the underlying biology and into causal mechanisms. Furthermore, a considerable amount of heritability still remains unexplain...Continue Reading

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  • Citations37

References

Mentioned in this Paper

Genome-Wide Association Study
Pathogenic Aspects
Biochemical Pathway
ORMDL3 gene
COMT gene
Meta-Analysis (Publications)
Pathogenesis
Immune System Diseases
Exons
Genome

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