Psychiatric genetics: progress amid controversy

  title={Psychiatric genetics: progress amid controversy},
  author={Margit Burmeister and Melvin G. McInnis and Sebastian Z{\"o}llner},
  journal={Nature Reviews Genetics},
Several psychiatric disorders — such as bipolar disorder, schizophrenia and autism — are highly heritable, yet identifying their genetic basis has been challenging, with most discoveries failing to be replicated. However, inroads have been made by the incorporation of intermediate traits (endophenotypes) and of environmental factors into genetic analyses, and through the identification of rare inherited variants and novel structural mutations. Current efforts aim to increase sample sizes by… 

New findings in the genetics of major psychoses

This review summarizes recent developments in genetic research into schizophrenia and bipolar disorder, and discusses possible future directions in this field.

Genetics of bipolar disorder

Genome-wide association studies have begun to appear for BPD, and more are in progress, with the aim of providing an unbiased approach and revealing novel biological mechanisms underlying BPD.

Genetics in psychiatry: Are the promises met?

  • B. Bondy
  • Medicine, Psychology
    The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry
  • 2011
Although the new data from GWAS are promising, they still do not meet initial expectations, identifying a “susceptibility gene”, and the incorporation of new approaches, as epigenetics, or gene-environmet interaction, is needed in future study designs.

Genetics in psychiatry: common variant association studies

Genetic risk for psychiatric conditions encompass rare variants, identified due to major effect, as well as common variants, the latter analyzed by association analyses, and guidelines for common variant association analyses are reviewed.

Human disease: Chipping away at psychiatric disorders

  • C. Gunter
  • Psychology, Medicine
    Nature Reviews Genetics
  • 2008
Increased variation in the patients is found, supporting recent publications, but backed up by a much larger sample size, and it’s still unclear exactly what this slight but significant increase in genomic variation means for disease, and how the increase arises.

Complex disease: Schizophrenia: missing heritability found?

  • C. Gunter
  • Psychology, Medicine
    Nature Reviews Genetics
  • 2009
Three new studies of schizophrenia illustrate some of the progress made by using GWA studies to investigate neuropsychiatric conditions, but they also highlight the utility of alternative approaches.

The genetics of bipolar disorder

Child and adolescent psychiatric genetics

It is becoming increasingly clear that very large sample sizes are required in order to enable genome wide significant findings, thus necessitating further large-scaled ascertainment schemes for the successful elucidation of the molecular genetics of childhood and adolescent psychiatric disorders.

Development of animal models for schizophrenia

This work has shown that the most common genomic structural rearrangements that are unequivocally associated with the development of schizophrenia, are de novo microdeletions of the 22q11.2 locus, and has made it possible to engineer genetically faithful, and thus etiologically valid, animal models of this schizophrenia susceptibility locus.



Rare Structural Variants Disrupt Multiple Genes in Neurodevelopmental Pathways in Schizophrenia

The results suggest that multiple, individually rare mutations altering genes in neurodevelopmental pathways contribute to schizophrenia, and disrupted genes disproportionately from signaling networks controlling neurodevelopment, including neuregulin and glutamate pathways.

Genes for schizophrenia and bipolar disorder? Implications for psychiatric nosology.

The pattern of findings emerging from genetic studies shows increasing evidence for an overlap in genetic susceptibility across the traditional classification categories-including association findings at DAOA(G72), DTNBP1 (dysbindin), COMT, BDNF, DISC1, and NRG1.

Molecular genetics of bipolar disorder.

  • N. CraddockI. Jones
  • Medicine, Psychology
    The British journal of psychiatry : the journal of mental science
  • 2001
It is almost certain that over the next few years the identification of bipolar susceptiblity genes will have a major impact on the understanding of disease pathophysiology.

Autism: in search of susceptibility genes.

The results of recent genetic linkage and candidate gene studies are reviewed in relation to the challenge of clinical and genetic heterogeneity, and prospects for the future of genetic research in autism are considered.

Molecular Mechanisms of Schizophrenia

Molecular findings suggest that a complex interplay between receptors, kinases, proteins and hormones is involved in schizophrenia and in a unifying hypothesis, different cascades merge into another that ultimately lead to the development of symptoms adherent to schizophrenic disorders.

Mapping autism risk loci using genetic linkage and chromosomal rearrangements

Linkage and copy number variation analyses implicate chromosome 11p12–p13 and neurexins, respectively, among other candidate loci, highlighting glutamate-related genes as promising candidates for contributing to ASDs.

Mouse models for psychiatric disorders.

Disease susceptibility genes for autism

Several genes have been proposed to play a role in susceptibility to autism and their potential role in the disorder are overviewed.

Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11.

The results show that a region of the genome that has been previously implicated by genetic linkage analysis can harbor genetic lesions that increase the susceptibility to schizophrenia.