Genetic heterogeneity, modifier genes, and quantitative phenotypes in psychiatric illness: searching for a framework

Fanous, Ayman H.; Kendler, Kenneth S.

doi:10.1038/sj.mp.4001571

Cited by 171 publications

(118 citation statements)

References 70 publications

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“…Although meta-analyses have not found a clear association between the Val158Met COMT polymorphism and vulnerability to schizophrenia (Fan et al, 2005;Munafo et al, 2005;Okochi et al, 2009), it is possible that it might still be related to schizophrenia as a disease modifying gene (Fanous and Kendler, 2005), via the putative intermediate phenotype of impaired cognitive function in the disorder. In support of this, the Val allele has been found to be associated with impaired performance on the Wisconsin Card Sorting Test (WCST), the n-back working memory task and other frontally mediated tasks in healthy subjects, patients with schizophrenia, and their first degree relatives (Aguilera et al, 2008;Caldu et al, 2007;de Frias et al, 2005;Diaz-Asper et al, 2008;Egan et al, 2001;Malhotra et al, 2002;Nolan et al, 2004;Rosa et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

COMT Val158Met polymorphism in relation to activation and de-activation in the prefrontal cortex: A study in patients with schizophrenia and healthy subjects

et al. 2010

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Section: Introductionmentioning

confidence: 99%

COMT Val158Met polymorphism in relation to activation and de-activation in the prefrontal cortex: A study in patients with schizophrenia and healthy subjects

et al. 2010

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“…We have previously argued that genes can affect the clinical presentation of schizophrenia in at least three ways [10]. First, genes may have a clinically nonspecific effect on illness susceptibility.…”

Section: Introductionmentioning

confidence: 99%

Genetics of clinical features and subtypes of schizophrenia: A review of the recent literature

Fanous

Kendler²

2008

Curr Psychiatry Rep

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Since its earliest descriptions, schizophrenia has been thought to be clinically heterogeneous. Symptomatic features and subtypes tend to aggregate in families, suggesting that genetic factors contribute to individual differences in illness presentation. Over the past 5 years, evidence from genetic linkage and association studies has mounted to suggest that some susceptibility genes are etiologic factors for more or less specific illness subtypes. Furthermore, modifier genes may affect clinical features dimensionally only after a given patient is already affected with the illness. In this paper, we review recent findings supporting the existence of such "modifier" genes. To date, DTNBP1 has provided the greatest evidence of illness modification, as associations with negative and cognitive symptoms and worse outcome have been published in independent samples. Future directions include using whole-genome association studies to search for genetic modifiers of schizophrenia.

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“…Modifier genes appear to influence disease characteristics but not disease liability [29]. Although considerable research has been devoted to polymorphisms associated with anxiety and mood disorders, overlap with other disorders has interfered with applications of the results to diagnosis or treatment in the same way that such approaches have been useful in cancer.…”

Section: Diagnosis and Assessmentmentioning

confidence: 99%

“…In psychiatric disorders, genetic factors interact with the environment to contribute both to illness susceptibility and clinical presentation [29]. Modifier genes appear to influence disease characteristics but not disease liability [29].…”

Section: Diagnosis and Assessmentmentioning

confidence: 99%

The Role of Pharmacogenomics to Guide Treatment in Mood and Anxiety Disorders

Dubovsky

2015

Curr Behav Neurosci Rep

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Interest has grown in genetic testing to personalize treatment approaches in psychiatry, especially mood disorders and to a lesser extent anxiety. However, numerous studies of genetic variants of metabolizing enzymes, along with fewer studies of single nucleotide polymorphisms of drug transporter proteins, receptors, and other putative drug targets such as neurotransmitter reuptake pumps and receptors, have reported contradictory findings that have not translated into practical, costeffective treatment recommendations. In this article, we review basic principles of genetic testing and highlight selected elements of genetic testing in cancer. We then critically review the current status of genetic research in pharmacokinetics and pharmacodynamics, as well as the few clinical trials that have been performed. After discussing the limited clinical applications of current research, we make recommendations for developing more clinically useful studies of cost-effective approaches to genetic testing in the treatment of mood and anxiety disorders.

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Genetic heterogeneity, modifier genes, and quantitative phenotypes in psychiatric illness: searching for a framework

Cited by 171 publications

References 70 publications

COMT Val158Met polymorphism in relation to activation and de-activation in the prefrontal cortex: A study in patients with schizophrenia and healthy subjects

COMT Val158Met polymorphism in relation to activation and de-activation in the prefrontal cortex: A study in patients with schizophrenia and healthy subjects

Genetics of clinical features and subtypes of schizophrenia: A review of the recent literature

The Role of Pharmacogenomics to Guide Treatment in Mood and Anxiety Disorders

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