A Genome-Wide Association Study of Schizophrenia Using Brain Activation as a Quantitative Phenotype

Background: Genome-wide association studies (GWASs) are increasingly used to identify risk genes for complex illnesses including schizophrenia. These studies may require thousands of subjects to obtain sufficient power. We present an alternative strategy with increased statistical power over a case-...

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Bibliographic Details
Published in:Schizophrenia bulletin 2009-01, Vol.35 (1), p.96-108
Main Authors: Potkin, Steven G., Turner, Jessica A., Guffanti, Guia, Lakatos, Anita, Fallon, James H., Nguyen, Dana D., Mathalon, Daniel, Ford, Judith, Lauriello, John, Macciardi, Fabio
Format: Article
Language:English
Subjects:
Adult
Aged
Brain - metabolism
Female
Genetic Testing - methods
Genome
Genome-Wide Association Study
Genotype
Germinal Center Kinases
Humans
Male
Membrane Proteins - genetics
Middle Aged
Nerve Tissue Proteins - genetics
Phenotype
Polymorphism, Single Nucleotide - genetics
Prefrontal Cortex - metabolism
Protein Serine-Threonine Kinases - genetics
Receptors, Immunologic - genetics
Roundabout Proteins
Schizophrenia - genetics
Schizophrenia - metabolism
Sodium-Potassium-Chloride Symporters - genetics
Solute Carrier Family 12, Member 2
Theme: Wide Spread Cortical Dysfunction in Schizophrenia: The FBIRN Imaging Consortium Guest Editors: Steven Potkin and Judith Ford
Young Adult
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Summary:Background: Genome-wide association studies (GWASs) are increasingly used to identify risk genes for complex illnesses including schizophrenia. These studies may require thousands of subjects to obtain sufficient power. We present an alternative strategy with increased statistical power over a case-control study that uses brain imaging as a quantitative trait (QT) in the context of a GWAS in schizophrenia. Methods: Sixty-four subjects with chronic schizophrenia and 74 matched controls were recruited from the Functional Biomedical Informatics Research Network (FBIRN) consortium. Subjects were genotyped using the Illumina HumanHap300 BeadArray and were scanned while performing a Sternberg Item Recognition Paradigm in which they learned and then recognized target sets of digits in an functional magnetic resonance imaging protocol. The QT was the mean blood oxygen level-dependent signal in the dorsolateral prefrontal cortex during the probe condition for a memory load of 3 items. Results: Three genes or chromosomal regions were identified by having 2 single-nucleotide polymorphisms (SNPs) each significant at P < 10−6 for the interaction between the imaging QT and the diagnosis (ROBO1-ROBO2, TNIK, and CTXN3-SLC12A2). Three other genes had a significant SNP at
ISSN:0586-7614
1745-1701
DOI:10.1093/schbul/sbn155