Schizophrenia is a major mental disorder that strikes in young adulthood and that has a heritability of 80-90%. Even with state-of-the-art treatment, schizophrenia often produces lifelong disability, creating a pressing need to delineate the heritable components so as to enable better classification, prognostication, and treatment. Despite the performance of many gene discovery studies, the genetic and phenotypic complexities of schizophrenia have largely confounded these efforts. To address this impasse, we will examine the etiology of schizophrenia by integrating exhaustive, high-quality genomic, phenotypic, and structural brain imaging data in a set of novel and imaginative aims. The strength of the application rests on the unique richness of our samples and the expertise of our investigative team. We bring together not just one, but two large, independent samples of individuals with schizophrenia and normal controls who have been scanned with high-resolution magnetic resonance brain imaging, exhaustively phenotyped, and who have provided DNA for genetic studies. Of these resources, it is the DNA that has yet to be fully utilized. By analyzing the DNA with state-of-the-art methods and a carefully crafted plan, we will substantially enhance the value of all the data domains. The research team comprises investigators with long histories of productivity in all pertinent areas-schizophrenia phenomenology, brain imaging, genomic technology, and biostatistics-and they are linked by a history of productive interaction and collaboration.

Public Health Relevance

Schizophrenia is a major mental disorder that is caused primarily by genetic factors and that is also associated with brain structure abnormalities. This study will attempt to identify schizophrenia susceptibility genes by using a wide array of genomic technology-microarrays, tests for genomic copy number variations, and others-and relating the resultant genetic data in an integrated fashion to both brain structure volumes and the core disorder itself.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH080128-01A2
Application #
7532706
Study Section
Genetics of Health and Disease Study Section (GHD)
Program Officer
Meinecke, Douglas L
Project Start
2009-05-14
Project End
2011-04-30
Budget Start
2009-05-14
Budget End
2010-04-30
Support Year
1
Fiscal Year
2009
Total Cost
$789,791
Indirect Cost
Name
University of Iowa
Department
Psychiatry
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Rudd, Danielle S; Axelsen, Michael; Epping, Eric A et al. (2014) A genome-wide CNV analysis of schizophrenia reveals a potential role for a multiple-hit model. Am J Med Genet B Neuropsychiatr Genet 165B:619-26
Onwuameze, O E; Nam, K W; Epping, E A et al. (2013) MAPK14 and CNR1 gene variant interactions: effects on brain volume deficits in schizophrenia patients with marijuana misuse. Psychol Med 43:619-31
Wassink, Thomas H; Epping, Eric A; Rudd, Danielle et al. (2012) Influence of ZNF804a on brain structure volumes and symptom severity in individuals with schizophrenia. Arch Gen Psychiatry 69:885-92
Meyer, Kacie J; Davis, Lea K; Schindler, Emily I et al. (2011) Genome-wide analysis of copy number variants in age-related macular degeneration. Hum Genet 129:91-100
Ho, Beng-Choon; Wassink, Thomas H; Ziebell, Steven et al. (2011) Cannabinoid receptor 1 gene polymorphisms and marijuana misuse interactions on white matter and cognitive deficits in schizophrenia. Schizophr Res 128:66-75
Hartz, Sarah M; Ho, Beng-Choon; Andreasen, Nancy C et al. (2010) G72 influences longitudinal change in frontal lobe volume in schizophrenia. Am J Med Genet B Neuropsychiatr Genet 153B:640-647