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December 2014

A Breakthrough in Schizophrenia Genetics

Author Affiliations
  • 1Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond
  • 2Department of Psychiatry, Virginia Commonwealth University, Richmond
  • 3Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond
  • 4MRC Centre for Psychiatric Genetics and Genomics, Cardiff University, Cardiff, Wales
JAMA Psychiatry. 2014;71(12):1319-1320. doi:10.1001/jamapsychiatry.2014.1776

The effort to understand the nature of the genetic risk for schizophrenia began more than 100 years ago. Since then, many studies have confirmed schizophrenia is strongly familial, largely as a result of genetic factors. As molecular genetic methods became available in the 1980s, serious interest turned to trying to identify the nature of this risk. It has proven a long and difficult road.

A recent article from the Schizophrenia Working Group of the Psychiatric Genomics Consortium (PGC) represents an important landmark on this journey.1 The study started with a primary sample of 49 nonoverlapping case-control samples (34 241 cases and 45 604 controls) and 3 family-based samples of European ancestry (1235 parent affected–offspring trios). For markers showing suggestive evidence for association, summary data were added based on genotypes from 1513 cases and 66 236 controls of European ancestry. Together, these samples identified 128 independent associations from 108 loci that met criteria for genome-wide significance. Eighty-three of these loci had not been previously reported. Multiple efforts were taken to ensure that these results were not artifactual and that most of the reported associations were true positives.

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