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Population-based case-control genetic study in schizophrenia

There is substantial indirect and, increasingly, direct evidence that the etiology of schizophrenia is strongly influenced by genetic effects.

Project description

In the brief history of the intensive efforts to dissect the genetic basis of complex human disorders like SCZ, few linkage or association studies have been designed with realistic statistical power. Moreover, in a review of over 101 genome scans, the key predictors of "success" were sample size and drawing subjects from one ancestral group. However, given limited resources, nearly all investigations of schizophrenia have chosen to devote considerable effort to phenotyping at the expense of sample size. In effect, the intention behind the effort we propose is to reverse the priorities of typical genetic studies of SCZ in attempting to ascertain a very large sample with accurate but inexpensive phenotypic determination. Therefore, we are currently collecting a very large sample of cases with SCZ along with well-matched controls. Both cases and controls are population-based and of Scandinavian ancestry. As a first step toward achieving this end, we have finished a pilot project in Uppsala county with the goal to provide proof-of-concept for a larger study.

The pilot project has the following specific aims:

  • Is it possible to perform a population-based genetic study from cases identified in Swedish registers?
  • How many cases with schizophrenia and unrelated controls identified in registers are willing to participate in genetic studies?
  • For how many patients with schizophrenia and unrelated controls are there available register data on environmental/non-genetic risk factors associated with schizophrenia?
  • How reliable are the schizophrenia diagnosis at discharge according to Hospital discharge register (in comparison with Diagnostic Interview for Genetic studies; DSM-IV; ICD-10)?
  • Support for the following candidate genes: candidate genes neuregulin (NRG1), dysbindin (DTNBP1), G-protein (RGS4) and catechol-O-methyltransferase (COMT)?
  • Genetical correlate to fetal growth aberration during the fetal stage or asphyxia

Project leader

Professor emerita

Christina Hultman


Main financing: Broad Institute, Harvard; Program support from Swedish Research Council Working Life and Social Research (FAS).


Institution Name
The Psychiatric and Neurodevelopmental Genetics Unit, Broad Institute, Harvard Medical School, Boston Pamela Sklar, Ed Scolnick
Department of Genetics, University of North Carolina, Chapel Hill Pat Sullivan
Department of Neuroscience, Uppsala University Frits-Axel Wiesel
Within the Department of Medical Epidemiology and Biostatistics Paul Lichtenstein