Physiogenomic analysis of localized fMRI brain activity in schizophrenia

Andreas Windemuth, Vince D. Calhoun, Godfrey D. Pearlson, Mohan Kocherla, Kanchana Jagannathan, Gualberto Ruaño

    Research output: Contribution to journalArticle

    Abstract

    The search for genetic factors associated with disease is complicated by the complexity of the biological pathways linking genotype and phenotype. This analytical complexity is particularly concerning in diseases historically lacking reliable diagnostic biological markers, such as schizophrenia and other mental disorders. We investigate the use of functional magnetic resonance imaging (fMRI) as an intermediate phenotype (endophenotype) to identify physiogenomic associations to schizophrenia. We screened 99 subjects, 30 subjects diagnosed with schizophrenia, 13 unaffected relatives of schizophrenia patients, and 56 unrelated controls, for gene polymorphisms associated with fMRI activation patterns at two locations in temporal and frontal lobes previously implied in schizophrenia. A total of 22 single nucleotide polymorphisms (SNPs) in 15 genes from the dopamine and serotonin neurotransmission pathways were genotyped in all subjects. We identified three SNPs in genes that are significantly associated with fMRI activity. SNPs of the dopamine beta-hydroxylase (DBH) gene and of the dopamine receptor D4 (DRD4) were associated with activity in the temporal and frontal lobes, respectively. One SNP of serotonin-3A receptor (HTR3A) was associated with temporal lobe activity. The results of this study support the physiogenomic analysis of neuroimaging data to discover associations between genotype and disease-related phenotypes.

    Original languageEnglish (US)
    Pages (from-to)877-888
    Number of pages12
    JournalAnnals of biomedical engineering
    Volume36
    Issue number6
    DOIs
    StatePublished - Jun 1 2008

    Keywords

    • Auditory oddball
    • Biomarkers
    • Dopamine receptors
    • Endophenotypes
    • Functional MRI
    • Genetics
    • Physiogenomics
    • Schizophrenia
    • Serotonin receptors

    ASJC Scopus subject areas

    • Biomedical Engineering

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