Abstract:
OBJECTIVES:Monozygotic twins with near-identical genotypes and discordance for complex diseases represent an exceptional resource to ascertain disease etiology. This strategy has been particularly effective with the availability of high-resolution complete individual genome sequencing. The challenge is using effective approaches to identify relevant differences that may cause or contribute toward disease discordance. PARTICIPANTS AND METHODS:This study carried out a VarScan2 bioinformatic analysis and a pathway analysis on whole-genome sequences from two sets of monozygotic twins. RESULTS:Variants were identified that were present in the affected twin, but not found in the unaffected twin. Such variations are expected to be de novo and originate during the independent development of the twins and may make them discordant for the disease. The genes and de novo variants identified in this experiment are compatible with their involvement in schizophrenia. Further analysis of the variants identified pathways including glutamate receptor signaling that have been implicated in this neurodevelopmental disease. CONCLUSION:The results support the polygenic nature of schizophrenia and the threshold model for its development. The results also show the effectiveness of VarScan2 to identify 'the needle in the hay stack' that may cause schizophrenia, specifically in the two patients. It offers a proof of principle for assessment of the genetic etiology of complex disorders where discordance of monozygotic twins is an established phenomenon.
journal_name
Psychiatr Genetjournal_title
Psychiatric geneticsauthors
Reble E,Castellani CA,Melka MG,O'Reilly R,Singh SMdoi
10.1097/YPG.0000000000000162subject
Has Abstractpub_date
2017-04-01 00:00:00pages
62-70issue
2eissn
0955-8829issn
1473-5873journal_volume
27pub_type
杂志文章abstract::The purpose of the present study was to investigate the association between the monocyte chemoattractant protein-1 (MCP-1) promoter -2518 polymorphism and schizophrenia. One hundred and twenty-three schizophrenic inpatients and 114 healthy controls participated in this study. Genotyping was performed by polymerase cha...
journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/01.ypg.0000128764.07344.06
更新日期:2004-06-01 00:00:00
abstract::3q29 deletion syndrome is caused by a heterozygous 1.6 Mb deletion on chromosome 3, which occurs in about 1 in 30 000 births. Phenotypic features of this syndrome include mild-to-moderate intellectual disability, autism spectrum disorder, slightly dysmorphic facial features, ataxic gait, and chest-wall deformity. Gast...
journal_title:Psychiatric genetics
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doi:10.1097/YPG.0000000000000256
更新日期:2020-08-01 00:00:00
abstract::P300 has been demonstrated abnormal for a variety of neuropsychiatric disorders, and heritability has been proposed. We analyzed the event-related potentials for three DRD2 genotype groups in 134 normal young females. The results demonstrate that there is no association for DRD2 genotype and P300 components. Our negat...
journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/00041444-200109000-00010
更新日期:2001-09-01 00:00:00
abstract:OBJECTIVES:The genetic basis of schizophrenia is obscure. In an XX male patient with schizophrenia we previously showed that one X;Y translocation breakpoint was in pseudoautosomal region 1 (PAR1) with the effect that the proximal segment of PAR1 from the PAR1 boundary to acetylserotonin N-methyl transferase (ASMT) dis...
journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/01.ypg.0000056683.89558.1c
更新日期:2003-06-01 00:00:00
abstract:OBJECTIVES:Susceptibility to heroin dependence is strongly influenced by genetic factors with heritability estimates as high as 0.7. A number of genes, as well as environmental factors, are likely to contribute to its etiology. Not all individuals who have ever tried heroin at some stage during their lifetime become de...
journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/YPG.0000000000000208
更新日期:2019-02-01 00:00:00
abstract::This study investigates the genetic association between methyl-CpG-binding domain (MBD) gene polymorphisms and schizophrenia. A total of 200 family trios consisting of fathers, mothers, and affected offspring with schizophrenia were recruited as our participants. Four tag SNPs on MBD1 (rs125555, rs140689, rs140687, an...
journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/YPG.0000000000000042
更新日期:2014-10-01 00:00:00
abstract::As an initial step for genome-wide association studies, we sought an association between schizophrenia and 34 microsatellite markers on chromosomes 19, 20, 21 and 22 by a case-control design. The samples examined for an association were 168 schizophrenic patients and 146 control subjects in the Japanese population. Th...
journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/00041444-200010030-00006
更新日期:2000-09-01 00:00:00
abstract::It is well established that approximately 50% of the variance in personality traits is genetic. The goal of this study was to investigate a relationship between personality traits and the T-182C polymorphism in the norepinephrine transporter gene. The participants included 115 healthy adults with no history of psychia...
journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/00041444-200506000-00012
更新日期:2005-06-01 00:00:00
abstract:OBJECTIVE:The dopamine D4 receptor (DRD4) is a candidate gene for increasing genetic susceptibility to schizophrenia. A recent study found that a -521C>T promoter base pair change affects transcriptional regulation of the DRD4 gene. The present study was designed to investigate the role of both the -521C>T single nucle...
journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/01.ypg.0000199446.54420.ff
更新日期:2006-08-01 00:00:00
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journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/YPG.0b013e3282fb003d
更新日期:2008-06-01 00:00:00
abstract::Since Lesch and colleagues reported an association between anxiety-related traits (Neuroticism) and a functional polymorphism in the serotonin transporter gene regulatory region (5-HTTLPR), there have been several reports on 5-HTTLPR and personality traits with both positive and negative results. The present study was...
journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/00041444-200010040-00002
更新日期:2000-12-01 00:00:00
abstract::Gilles de la Tourette syndrome (GTS) (MIM 137580) is a complex neuropsychiatric disorder probably originating from a disturbed interplay of several neurotransmitter systems in the prefrontal-limbic-basal ganglia loop. Polygenetic multifactorial inheritance has been postulated; nevertheless, no confirmed susceptible ge...
journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/YPG.0b013e32833511ce
更新日期:2010-02-01 00:00:00
abstract:OBJECTIVE:Biological evidence in both human and animal studies suggests α7 neuronal nicotinic acetylcholine receptor subunit gene (CHRNA7) as a suitable functional candidate for genetic studies in psychiatric populations. This gene maps to chromosome 15q13-14, a major linkage hotspot for schizophrenia (SCH) and bipolar...
journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/YPG.0b013e32833a9b7a
更新日期:2010-12-01 00:00:00
abstract:BACKGROUND:A long-term controversy exists on whether or not major psychotic disorders can be discretely divided into two groups, for example, schizophrenia and bipolar disorder. Many genes and polymorphisms have been studied for a role in both disorders, including the Val66Met (also known as rs 6265 or G196A) variant o...
journal_title:Psychiatric genetics
pub_type: 杂志文章,meta分析
doi:10.1097/YPG.0b013e32801da2e2
更新日期:2007-06-01 00:00:00
abstract::Since 1969, several classical linkage studies suggested an X-chromosome locus for bipolar affective disorder. However, methods using highly polymorphic DNA markers have provided conflicting evidence for linkage, and an X-chromosomal locus for bipolar disorder remains controversial. More recently, Pekkarinen et al. (19...
journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/00041444-199800830-00008
更新日期:1998-10-01 00:00:00
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journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/00041444-200106000-00003
更新日期:2001-06-01 00:00:00
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journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/YPG.0000000000000228
更新日期:2019-12-01 00:00:00
abstract:INTRODUCTION:The importance of dopamine D2 receptors (DRD2) for central nervous dopaminergic signalling makes variants in the DRD2 gene potential modulators of the risk or course of various behavioural, psychiatric or neurologic diseases (e.g. addiction, schizophrenia, Parkinson's disease). We developed Pyrosequencing ...
journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/YPG.0b013e32832d0941
更新日期:2009-10-01 00:00:00
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journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/ypg.0b013e32832cec89
更新日期:2009-08-01 00:00:00
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journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/YPG.0b013e32832a4f7b
更新日期:2009-06-01 00:00:00
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journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/YPG.0000000000000259
更新日期:2020-10-01 00:00:00
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journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/01.ypg.0000199449.07786.7d
更新日期:2006-06-01 00:00:00
abstract::The glycine receptor, which is a member of the ligand-gated ion channel superfamily, mediates synaptic inhibition in the spinal cord and other brain regions. This superfamily has been implicated in the pathogenesis of schizophrenia and other psychiatric diseases. The complete coding sequence and splice junctions of th...
journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/00041444-200103000-00009
更新日期:2001-03-01 00:00:00
abstract:OBJECTIVE:To apply phenotypic and statistical methods designed to account for heterogeneity to linkage analyses of the autism Collaborative Linkage Study of Autism (CLSA) affected sibling pair families. METHOD:The CLSA contains two sets of 57 families each; Set 1 has been analyzed previously, whereas this study presen...
journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/YPG.0b013e3282f9b48e
更新日期:2008-04-01 00:00:00
abstract:OBJECTIVE:Recent research implicates the catechol-O-methyltransferase (COMT) ValMet polymorphism in stress sensitivity, through modulation of hypothalamic-pituitary-adrenal (HPA) function. In healthy samples, Met homozygosity has been associated with greater HPA activity (i.e., cortisol) and stress sensitivity, though ...
journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/YPG.0b013e32833a1ff3
更新日期:2010-08-01 00:00:00
abstract:OBJECTIVES:Autism is a neurodevelopmental disorder, and genetic factors play an important role in its pathogenesis. Earlier findings suggest the CNTNAP2 as a predisposition locus of autism, but no study has been carried out on the possible association of CNTNAP2 with autism in the Chinese Han population. METHODS:In th...
journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/YPG.0b013e32833a216f
更新日期:2010-06-01 00:00:00
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journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/YPG.0000000000000266
更新日期:2020-12-01 00:00:00
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journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/YPG.0b013e32834371e8
更新日期:2011-10-01 00:00:00
abstract:OBJECTIVE:To examine the heritabilities of symptoms of posttraumatic stress disorder (PTSD), anxiety, depression, and the shared genetic component of these symptoms among family members exposed to the 1988 Spitak earthquake in Armenia. METHODS:Two hundred members of 12 multigenerational families exposed to the Spitak ...
journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/YPG.0b013e3283060f48
更新日期:2008-12-01 00:00:00
abstract::Phenylthiocarbamide (PTC) taste sensitivity is an inherited trait determined primarily by allelic variation of the taste-receptor gene TAS2R38 on chromosome 7q. Results of prior studies examining the ability to taste PTC in patients with schizophrenia have been mixed because of the difficulties in measuring PTC taste ...
journal_title:Psychiatric genetics
pub_type: 杂志文章
doi:10.1097/YPG.0b013e32835863f0
更新日期:2012-12-01 00:00:00