The cause 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-á) 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, 4 (AKT1 (3 SNPs), BDNF (2 SNPs), DTNBP1 (1 SNP) and GRM3 (1 SNP)) showed significant evidence for gene-by-environment interaction (LRT p-values ranged from 0.011-0.037). Although our sample size was modest and therefore 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.
Kristin K. Nicodemus1, Stefano Marenco1, Adam J. Batten.1, Radhakrishna Vakkalanka1, Michael F. Egan1, Richard E. Straub1, Daniel R. Weinberger1
1 Genes, Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Room 4S-235, 10 Center Drive, Bethesda, Maryland, 20892, USA
Citation source: Molecular Psychiatry advance online publication 15 JANUARY 2008
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Corresponding author: Daniel Weinberger, M.D.
Genes, Cognition and Psychosis Program
IRP, NIMH, NIH
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Bethesda, Maryland 20892
USA
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Email: weinberd@mail.nih.gov
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Molecular Psychiatry