Genes for schizophrenia? Recent findings and their pathophysiological implications

  title={Genes for schizophrenia? Recent findings and their pathophysiological implications},
  author={Paul J. Harrison and Michael John Owen},
  journal={The Lancet},

Clinical impact of recently detected susceptibility genes for schizophrenia

There are now at least three very strong candidates: the gene for dysbindin (DINBP1), the genes for neuregulin-1 (NRG1), and a less well-understood gene locus, G72/G30, which are likely to influence manifestations of schizophrenia.

The genes for schizophrenia: Finally a breakthrough?

Though credible evidence is available for all of these genes, it is strongest for NRG1 and DTNBP1, and further studies, particularly exhaustive analyses of all polymorphisms at each locus, meta-analyses, and investigations of the likely function of risk alleles (variants) are desirable.

Schizophrenia: genes at last?

Recent genetic findings in schizophrenia and their therapeutic relevance

This review summarises recent schizophrenia genetic findings and some key issues they raise, particularly with regard to their implications for identifying and validating novel drug targets.

Recent advances in the genetics of schizophrenia.

The ability of positional genetics to implicate novel genes and pathways will open up new vistas for neurobiological research, and all the signs are that genetic research is poised to deliver crucial insights into the nature of schizophrenia.

In search of susceptibility genes for schizophrenia

An association of schizophrenia with the gene RGS4 (regulator of G protein signaling 4), a modulator of the function of multiple G-protein-linked neurotransmitter receptors, was identified andGene expression analyses of postmortem cerebral cortex indicate that the transcription of R GS4 is diminished within schizophrenia.

The molecular genetics of schizophrenia: new findings promise new insights

The ability of positional genetics to implicate novel genes and pathways will open up new vistas for neurobiological research, and all the signs are that it is now poised to deliver crucial insights into the nature of schizophrenia.

Genomic approaches to schizophrenia.

  • M. Owen
  • Medicine, Psychology
    Clinical therapeutics
  • 2005

Searching for inherited causes for schizophrenia: has progress been made?

This book currently outlines the conclusions drawn subsequent to the 5th meeting of investigators on “Search for the Causes of Schizophrenia”, and concludes that mathematical genetic modeling confirms the heritable component for schizophrenia.

Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence

This review critically summarizes the neuropathology and genetics of schizophrenia, the relationship between them, and speculates on their functional convergence via an influence upon synaptic plasticity and the development and stabilization of cortical microcircuitry.



The discovery of susceptibility genes for mental disorders

  • C. R. Cloninger
  • Psychology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 2002
A new human gene is described, G72, on chromosome 13q34 that interacts with the gene for d-amino acid oxidase (DAAO) on 12q24 to regulate glutaminergic signaling through the N- methyl-d-aspartate (NMDA) receptor pathway, the first discovery of a specific gene that also provides a pathogenic molecular mechanism that can account for the major symptoms of a psychiatric disorder.

Neuregulin 1 and susceptibility to schizophrenia.

The results of a genomewide scan of schizophrenia families in Iceland show that schizophrenia maps to chromosome 8p, and extensive fine-mapping of the 8p locus and haplotype-association analysis identifies neuregulin 1 (NRG1) as a candidate gene for schizophrenia.

Association and linkage analyses of RGS4 polymorphisms in schizophrenia.

The results illustrate the potential power of combining gene expression profiling and genomic analyses to identify susceptibility genes for genetically complex disorders.

A highly significant association between a COMT haplotype and schizophrenia.

An efficient approach to gene discovery is reported that found a highly significant association between schizophrenia and a COMT haplotype and can be widely implemented for the genetic dissection of other common diseases.

Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia.

Family-based association analysis of 36 simple sequence-length-polymorphism markers and of 17 SNP markers implicated two regions, separated by approximately 7 Mb, that are strongly associated with schizophrenia, and it is concluded that further investigation of dysbindin is warranted.

Schizophrenia as a disorder of neurodevelopment.

These findings suggest that combinatorial genetic and environmental factors, which disturb a normal developmental course early in life, result in molecular and histogenic responses that cumulatively lead to different developmental trajectories and the clinical phenotype recognized as schizophrenia.

Genetic and physiological data implicating the new human gene G72 and the gene for d-amino acid oxidase in schizophrenia

A map of 191 single-nucleotide polymorphism (SNPs) was built across a 5-Mb segment from chromosome 13q34 that has been genetically linked to schizophrenia, pointing to the involvement of this N-methyl-d-aspartate receptor regulation pathway in schizophrenia.

Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia

  • Hui LiuS. Heath M. Karayiorgou
  • Psychology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 2002
In three independent samples, evidence is provided for a contribution of the PRODH2/DGCR6 locus in 22q11-associated schizophrenia and an unusual pattern of PRODh2 gene variation that mimics the sequence of a linked pseudogene is uncovered.

The neuropathology of schizophrenia. A critical review of the data and their interpretation.

Functional imaging data indicate that the pathophysiology of schizophrenia reflects aberrant activity in, and integration of, the components of distributed circuits involving the prefrontal cortex, hippocampus and certain subcortical structures.

Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia

Simulations demonstrated that the type I error rate was at least as low as that for a single genome scan and thus genome-wide significance criteria may be applied, and power to detect linkage wasat least as high as the power of pooling the data from all the studies.