Serious obstetric complications interact with hypoxia-regulated/vascular-expression genes to influence schizophrenia risk

The etiology of schizophrenia is thought to include both epistasis and gene-environment interactions. We sought to test whether a set of schizophrenia candidate genes regulated by hypoxia or involved in vascular function in the brain (AKT1, BDNF, CAPON, CHRNA7, COMT, DTNBP1, GAD1, GRM3, NOTCH4, NRG1...

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Published inMolecular psychiatry Vol. 13; no. 9; pp. 873 - 877
Main Authors Nicodemus, K K, Marenco, S, Batten, A J, Vakkalanka, R, Egan, M F, Straub, R E, Weinberger, D R
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.09.2008
Nature Publishing Group
Subjects
Adult and adolescent clinical studies
AKT1 protein
Behavioral Sciences
Biological and medical sciences
Biological Psychology
Brain-derived neurotrophic factor
Cesarean section
Diagnosis
Epistasis
Etiology
Families & family life
Family Health
Female
Fetuses
Gene Expression Regulation - physiology
Genes
Genetic aspects
Gestational age
Humans
Hypoxia
Hypoxia-Ischemia, Brain - embryology
Hypoxia-Ischemia, Brain - genetics
Hypoxia-Ischemia, Brain - physiopathology
Linkage Disequilibrium
Logistic Models
Male
Medical sciences
Medicine
Medicine & Public Health
Mental disorders
Mental health
Neurosciences
Obstetric Labor Complications
Obstetrics
Odds Ratio
original-article
Pharmacotherapy
Physiological aspects
Polymorphism, Single Nucleotide
Pregnancy
Proto-Oncogene Proteins c-akt - genetics
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Psychoses
Psychosis
Regression analysis
Risk Factors
Schizophrenia
Schizophrenia - etiology
Schizophrenia - genetics
Single-nucleotide polymorphism
Statistical analysis
Surveys and Questionnaires
Tumor necrosis factor-α
United States
United States > US
obstetric complications
hypoxia
AKT1
schizophrenia
genes
Psychosis
Oxygen
Gene
Schizophrenia
Genetics
Complication
Hypoxia
Genetic determinism
Obstetrics
Online AccessGet full text

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Abstract The etiology of schizophrenia is thought to include both epistasis and gene-environment interactions. We sought to test whether a set of schizophrenia candidate genes regulated by hypoxia or involved in vascular function in the brain (AKT1, BDNF, CAPON, CHRNA7, COMT, DTNBP1, GAD1, GRM3, NOTCH4, NRG1, PRODH, RGS4, TNF-α) interacted with serious obstetric complications to influence risk for schizophrenia. A family-based study of transmission disequilibrium was conducted in 116 trios. Twenty-nine probands had at least one serious obstetric complication (OC) using the McNeil-Sjostrom Scale, and many of the OCs reported were associated with the potential for fetal hypoxia. Analyses were conducted using conditional logistic regression and a likelihood ratio test (LRT) between nested models was performed to assess significance. Of the 13 genes examined, four (AKT1 (three SNPs), BDNF (two SNPs), DTNBP1 (one SNP) and GRM3 (one SNP)) showed significant evidence for gene-by-environment interaction (LRT P -values ranged from 0.011 to 0.037). Although our sample size was modest and the power to detect interactions was limited, we report significant evidence for genes involved in neurovascular function or regulated by hypoxia interacting with the presence of serious obstetric complications to increase risk for schizophrenia.
AbstractList The etiology of schizophrenia is thought to include both epistasis and gene-environment interactions. We sought to test whether a set of schizophrenia candidate genes regulated by hypoxia or involved in vascular function in the brain (AKT1, BDNF, CAPON, CHRNA7, COMT, DTNBP1, GAD1, GRM3, NOTCH4, NRG1, PRODH, RGS4, TNF- alpha ) interacted with serious obstetric complications to influence risk for schizophrenia. A family-based study of transmission disequilibrium was conducted in 116 trios. Twenty-nine probands had at least one serious obstetric complication (OC) using the McNeil-Sjostrom Scale, and many of the OCs reported were associated with the potential for fetal hypoxia. Analyses were conducted using conditional logistic regression and a likelihood ratio test (LRT) between nested models was performed to assess significance. Of the 13 genes examined, four (AKT1 (three SNPs), BDNF (two SNPs), DTNBP1 (one SNP) and GRM3 (one SNP)) showed significant evidence for gene-by-environment interaction (LRT P-values ranged from 0.011 to 0.037). Although our sample size was modest and the power to detect interactions was limited, we report significant evidence for genes involved in neurovascular function or regulated by hypoxia interacting with the presence of serious obstetric complications to increase risk for schizophrenia.Molecular Psychiatry (2008) 13, 873-877; doi:10.1038/sj.mp.4002153; published online 15 January 2008
The etiology of schizophrenia is thought to include both epistasis and gene-environment interactions. We sought to test whether a set of schizophrenia candidate genes regulated by hypoxia or involved in vascular function in the brain (AKT1, BDNF, CAPON, CHRNA7, COMT, DTNBP1, GAD1, GRM3, NOTCH4, NRG1, PRODH, RGS4, TNF-alpha) interacted with serious obstetric complications to influence risk for schizophrenia. A family-based study of transmission disequilibrium was conducted in 116 trios. Twenty-nine probands had at least one serious obstetric complication (OC) using the McNeil-Sjostrom Scale, and many of the OCs reported were associated with the potential for fetal hypoxia. Analyses were conducted using conditional logistic regression and a likelihood ratio test (LRT) between nested models was performed to assess significance. Of the 13 genes examined, four (AKT1 (three SNPs), BDNF (two SNPs), DTNBP1 (one SNP) and GRM3 (one SNP)) showed significant evidence for gene-by-environment interaction (LRT P-values ranged from 0.011 to 0.037). Although our sample size was modest and the power to detect interactions was limited, we report significant evidence for genes involved in neurovascular function or regulated by hypoxia interacting with the presence of serious obstetric complications to increase risk for schizophrenia.The etiology of schizophrenia is thought to include both epistasis and gene-environment interactions. We sought to test whether a set of schizophrenia candidate genes regulated by hypoxia or involved in vascular function in the brain (AKT1, BDNF, CAPON, CHRNA7, COMT, DTNBP1, GAD1, GRM3, NOTCH4, NRG1, PRODH, RGS4, TNF-alpha) interacted with serious obstetric complications to influence risk for schizophrenia. A family-based study of transmission disequilibrium was conducted in 116 trios. Twenty-nine probands had at least one serious obstetric complication (OC) using the McNeil-Sjostrom Scale, and many of the OCs reported were associated with the potential for fetal hypoxia. Analyses were conducted using conditional logistic regression and a likelihood ratio test (LRT) between nested models was performed to assess significance. Of the 13 genes examined, four (AKT1 (three SNPs), BDNF (two SNPs), DTNBP1 (one SNP) and GRM3 (one SNP)) showed significant evidence for gene-by-environment interaction (LRT P-values ranged from 0.011 to 0.037). Although our sample size was modest and the power to detect interactions was limited, we report significant evidence for genes involved in neurovascular function or regulated by hypoxia interacting with the presence of serious obstetric complications to increase risk for schizophrenia.
The etiology of schizophrenia is thought to include both epistasis and gene-environment interactions. We sought to test whether a set of schizophrenia candidate genes regulated by hypoxia or involved in vascular function in the brain (AKT1, BDNF, CAPON, CHRNA7, COMT, DTNBP1, GAD1, GRM3, NOTCH4, NRG1, PRODH, RGS4, TNF-alpha) interacted with serious obstetric complications to influence risk for schizophrenia. A family-based study of transmission disequilibrium was conducted in 116 trios. Twenty-nine probands had at least one serious obstetric complication (OC) using the McNeil-Sjostrom Scale, and many of the OCs reported were associated with the potential for fetal hypoxia. Analyses were conducted using conditional logistic regression and a likelihood ratio test (LRT) between nested models was performed to assess significance. Of the 13 genes examined, four (AKT1 (three SNPs), BDNF (two SNPs), DTNBP1 (one SNP) and GRM3 (one SNP)) showed significant evidence for gene-by-environment interaction (LRT P-values ranged from 0.011 to 0.037). Although our sample size was modest and the power to detect interactions was limited, we report significant evidence for genes involved in neurovascular function or regulated by hypoxia interacting with the presence of serious obstetric complications to increase risk for schizophrenia.
The etiology of schizophrenia is thought to include both epistasis and gene-environment interactions. We sought to test whether a set of schizophrenia candidate genes regulated by hypoxia or involved in vascular function in the brain (AKT1, BDNF, CAPON, CHRNA7, COMT, DTNBP1, GAD1, GRM3, NOTCH4, NRG1, PRODH, RGS4, TNF-α) interacted with serious obstetric complications to influence risk for schizophrenia. A family-based study of transmission disequilibrium was conducted in 116 trios. Twenty-nine probands had at least one serious obstetric complication (OC) using the McNeil-Sjostrom Scale, and many of the OCs reported were associated with the potential for fetal hypoxia. Analyses were conducted using conditional logistic regression and a likelihood ratio test (LRT) between nested models was performed to assess significance. Of the 13 genes examined, four (AKT1 (three SNPs), BDNF (two SNPs), DTNBP1 (one SNP) and GRM3 (one SNP)) showed significant evidence for gene-by-environment interaction (LRT P -values ranged from 0.011 to 0.037). Although our sample size was modest and the power to detect interactions was limited, we report significant evidence for genes involved in neurovascular function or regulated by hypoxia interacting with the presence of serious obstetric complications to increase risk for schizophrenia.
The etiology of schizophrenia is thought to include both epistasis and gene-environment interactions. We sought to test whether a set of schizophrenia candidate genes regulated by hypoxia or involved in vascular function in the brain (AKT1, BDNF, CAPON, CHRNA7, COMT, DTNBP1, GAD1, GRM3, NOTCH4, NRG1, PRODH, RGS4, TNF-α) interacted with serious obstetric complications to influence risk for schizophrenia. A family-based study of transmission disequilibrium was conducted in 116 trios. Twenty-nine probands had at least one serious obstetric complication (OC) using the McNeil-Sjostrom Scale, and many of the OCs reported were associated with the potential for fetal hypoxia. Analyses were conducted using conditional logistic regression and a likelihood ratio test (LRT) between nested models was performed to assess significance. Of the 13 genes examined, four (AKT1 (three SNPs), BDNF (two SNPs), DTNBP1 (one SNP) and GRM3 (one SNP)) showed significant evidence for gene-by-environment interaction (LRT P-values ranged from 0.011 to 0.037). Although our sample size was modest and the power to detect interactions was limited, we report significant evidence for genes involved in neurovascular function or regulated by hypoxia interacting with the presence of serious obstetric complications to increase risk for schizophrenia.
Audience Academic
Author Nicodemus, K K
Batten, A J
Marenco, S
Egan, M F
Weinberger, D R
Vakkalanka, R
Straub, R E
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  surname: Nicodemus
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  organization: Genes, Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health
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  fullname: Batten, A J
  organization: Genes, Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health
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  surname: Vakkalanka
  fullname: Vakkalanka, R
  organization: Genes, Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health
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  surname: Weinberger
  fullname: Weinberger, D R
  email: weinberd@mail.nih.gov
  organization: Genes, Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health
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https://www.ncbi.nlm.nih.gov/pubmed/18195713$$D View this record in MEDLINE/PubMed
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2008 INIST-CNRS
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IsPeerReviewed true
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Issue 9
Keywords obstetric complications
hypoxia
AKT1
schizophrenia
genes
Psychosis
Oxygen
Gene
Schizophrenia
Genetics
Complication
Hypoxia
Genetic determinism
Obstetrics
Language English
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Snippet The etiology of schizophrenia is thought to include both epistasis and gene-environment interactions. We sought to test whether a set of schizophrenia...
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SubjectTerms Adult and adolescent clinical studies
AKT1 protein
Behavioral Sciences
Biological and medical sciences
Biological Psychology
Brain-derived neurotrophic factor
Cesarean section
Diagnosis
Epistasis
Etiology
Families & family life
Family Health
Female
Fetuses
Gene Expression Regulation - physiology
Genes
Genetic aspects
Gestational age
Humans
Hypoxia
Hypoxia-Ischemia, Brain - embryology
Hypoxia-Ischemia, Brain - genetics
Hypoxia-Ischemia, Brain - physiopathology
Linkage Disequilibrium
Logistic Models
Male
Medical sciences
Medicine
Medicine & Public Health
Mental disorders
Mental health
Neurosciences
Obstetric Labor Complications
Obstetrics
Odds Ratio
original-article
Pharmacotherapy
Physiological aspects
Polymorphism, Single Nucleotide
Pregnancy
Proto-Oncogene Proteins c-akt - genetics
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Psychoses
Psychosis
Regression analysis
Risk Factors
Schizophrenia
Schizophrenia - etiology
Schizophrenia - genetics
Single-nucleotide polymorphism
Statistical analysis
Surveys and Questionnaires
Tumor necrosis factor-α
Title Serious obstetric complications interact with hypoxia-regulated/vascular-expression genes to influence schizophrenia risk
URI https://link.springer.com/article/10.1038/sj.mp.4002153
https://www.ncbi.nlm.nih.gov/pubmed/18195713
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Volume 13
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