Schizophrenia: an example of complex genetic disease

Thibaut, Florence

doi:10.1080/15622970600994313

Cited by 12 publications

(10 citation statements)

References 18 publications

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“…The heritability has been estimated to be between 63 and 85%. Other risk factors include: male gender, advanced paternal age, perinatal events, infl uenza or other infections in second pregnancy trimester, seasonal birth in spring, or drug use (Torrey et al 1997;Brown et al 2004;Thibaut, 2006). In complex and multifactorial diseases such as schizophrenia, there is a low correlation between the genotype and the phenotype.…”

Section: Neurophysiological Biomarkers and Endophenotypes In Schizophmentioning

confidence: 99%

Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for biomarkers and endophenotypes of schizophrenia part I: Neurophysiology

Thibaut

Boutros

Jarema

et al. 2015

The World Journal of Biological Psychiatry

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The neurophysiological components that have been proposed as biomarkers or as endophenotypes for schizophrenia can be measured through electroencephalography (EEG) and magnetoencephalography (MEG), transcranial magnetic stimulation (TMS), polysomnography (PSG), registration of event-related potentials (ERPs), assessment of smooth pursuit eye movements (SPEM) and antisaccade paradigms. Most of them demonstrate deficits in schizophrenia, show at least moderate stability over time and do not depend on clinical status, which means that they fulfil the criteria as valid endophenotypes for genetic studies. Deficits in cortical inhibition and plasticity measured using non-invasive brain stimulation techniques seem promising markers of outcome and prognosis. However the utility of these markers as biomarkers for predicting conversion to psychosis, response to treatments, or for tracking disease progression needs to be further studied.

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Section: Neurophysiological Biomarkers and Endophenotypes In Schizophmentioning

confidence: 99%

Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for biomarkers and endophenotypes of schizophrenia part I: Neurophysiology

Thibaut

Boutros

Jarema

et al. 2015

The World Journal of Biological Psychiatry

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“…Schizophrenia (SZ) is a highly heritable yet complex multifactorial psychiatric disorder (Braff, 2015; Braff et al, 2007b; Thibaut, 2006). Locating genes that are associated with schizophrenia is a key step in identifying potentially remediable biological pathways for the development of novel treatments.…”

Section: Introductionmentioning

confidence: 99%

Prioritizing schizophrenia endophenotypes for future genetic studies: An example using data from the COGS-1 family study

Millard

Shofer

Braff

et al. 2016

Schizophrenia Research

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Past studies describe numerous endophenotypes associated with schizophrenia (SZ), but many endophenotypes may overlap in information they provide, and few studies have investigated the utility of a multivariate index to improve discrimination between SZ and healthy community comparison subjects (CCS). We investigated 16 endophenotypes from the first phase of the Consortium on the Genetics of Schizophrenia, a large, multi-site family study, to determine whether a subset could distinguish SZ probands and CCS just as well as using all 16. Participants included 345 SZ probands and 517 CCS with a valid measure for at least one endophenotype. We used both logistic regression and random forest models to choose a subset of endophenotypes, adjusting for age, gender, smoking status, site, parent education, and the reading subtest of the Wide Range Achievement Test. As a sensitivity analysis, we re-fit models using multiple imputations to determine the effect of missing values. We identified four important endophenotypes: antisaccade, Continuous Performance Test-Identical Pairs 3-digit version, California Verbal Learning Test, and emotion identification. The logistic regression model that used just these four endophenotypes produced essentially the same results as the model that used all 16 (84% vs. 85% accuracy). While a subset of endophenotypes cannot replace clinical diagnosis nor encompass the complexity of the disease, it can aid in the design of future endophenotypic and genetic studies by reducing study cost and subject burden, simplifying sample enrichment, and improving statistical power of locating genetic regions associated with schizophrenia that may be the easiest to identify initially.

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“…Schizophrenia is a complex trait with a strong genetic background [29,30] whose detailed pathogenesis remains unclear. Recently, several studies have described the epiphenomenon that the incidence of cancer is decreased in patients with schizophrenia compared with that in the general population [31].…”

Section: Discussionmentioning

confidence: 99%

“…Schizophrenia is a multi-factorial genetic disease [29,30] that is suggested to be caused by the synergistic effect of different genetic variants [37]. Previously, we have reported that the long form alleles of the uVNTR polymorphism in DRD4 might a risk factor for vulnerability to schizophrenia [25].…”

Section: Discussionmentioning

confidence: 99%

Association of DRD4 uVNTR and TP53 codon 72 polymorphisms with schizophrenia: a case-control study

et al. 2009

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BackgroundThe tumour supressor gene TP53 is thought to be involved in neural apoptosis. The polymorphism at codon 72 in TP53 and the long form variants of the upstream variable number of tandem repeats (uVNTR) polymorphism in the dopamine D4 receptor (DRD4) gene are reported to confer susceptibility to schizophrenia.MethodsWe recruited 934 patients with schizophrenia and 433 healthy individuals, and genotyped the locus of the TP53 codon 72 and DRD4 uVNTR polymorphisms by combining the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) with direct sequencing.ResultsNo significant differences were found in the frequency of the genotype of the TP53 codon72 polymorphism between patients with schizophrenia and their controls. However, the long form alleles (≥ 5 repeats) of the DRD4 uVNTR polymorphism were more frequent in patients with schizophrenia than in controls (p = 0.001). Hence, this class of alleles might be a risk factor for enhanced vulnerability to schizophrenia (odds ratio = 3.189, 95% confidence interval = 1.535-6.622). In the logistic regression analysis, the long form variants of the DRD4 polymorphism did predict schizophrenia after the contributions of the age and gender of the subjects were included (p = 0.036, OR = 2.319), but the CC and GG genotypes of the codon 72 polymorphism of TP53 did not.ConclusionsThe long form variants of the uVNTR polymorphism in DRD4 were associated with schizophrenia, in a manner that was independent of the TP53 codon 72 polymorphism. In addition, given that the genetic effect of the TP53 codon 72 polymorphism on the risk of developing schizophrenia was very small, this polymorphism is unlikely to be associated with schizophrenia. The roles that other single nucleotide polymorphisms (SNPs) in the TP53 gene or in other apoptosis-related genes play in the synaptic dysfunction involved in the pathogenesis of schizophrenia should be investigated.

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Schizophrenia: an example of complex genetic disease

Cited by 12 publications

References 18 publications

Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for biomarkers and endophenotypes of schizophrenia part I: Neurophysiology

Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for biomarkers and endophenotypes of schizophrenia part I: Neurophysiology

Prioritizing schizophrenia endophenotypes for future genetic studies: An example using data from the COGS-1 family study

Association of DRD4 uVNTR and TP53 codon 72 polymorphisms with schizophrenia: a case-control study

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