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The Consortium on the Genetics of Schizophrenia

Tiffany A. Greenwood, PhD; David L. Braff, MD; Gregory A. Light, PhD; Kristin S. Cadenhead, MD; Monica E. Calkins, PhD; Dorcas J. Dobie, MD; Robert Freedman, MD; Michael F. Green, PhD; Raquel E. Gur, MD, PhD; Ruben C. Gur, PhD; Jim Mintz, PhD; Keith H. Nuechterlein, PhD; Ann Olincy, MD; Allen D. Radant, MD; Larry J. Seidman, PhD; Larry J. Siever, MD; Jeremy M. Silverman, PhD; William S. Stone, PhD; Neal R. Swerdlow, MD, PhD; Debby W. Tsuang, MD, MSc; Ming T. Tsuang, MD, PhD; Bruce I. Turetsky, MD; Nicholas J. Schork, PhD

Arch Gen Psychiatry. 2007;64(11):1242-1250.

Context  Exploration of the genetic architecture of specific endophenotypes may be a powerful strategy for understanding the genetic basis of schizophrenia.

Objective  To characterize the genetic architecture of some key endophenotypic measures selected for their reported heritabilities in schizophrenia.

Design  Family-based heritability study.

Setting  Seven sites across the United States.

Participants  At the time of these initial data analyses, the members of 183 nuclear families ascertained through probands with schizophrenia had been assessed for these endophenotypes.

Main Outcome Measures  Variance component models were used to assess the heritability of and the environmental and genetic correlations among the endophenotypes. The Consortium on the Genetics of Schizophrenia assesses the neurophysiologic measures of prepulse inhibition of acoustic startle, P50 event-related potential suppression, and the antisaccade task for eye movements and the neurocognitive measures of the Continuous Performance Test (Degraded Stimulus version), the California Verbal Learning Test, the Letter-Number Sequencing test, and 6 measures from the University of Pennsylvania Computerized Neurocognitive Battery. The heritabilities of these 12 measures are the focus of this article.

Results  All of the endophenotypes and the University of Pennsylvania Computerized Neurocognitive Battery measures were found to be significantly heritable (P  .005), with heritabilities ranging from 24% to 55%. Significant environmental and genetic correlations were also observed between many of the endophenotypic measures.

Conclusion  This is the first large-scale, multisite, family-based heritability study of a collection of endophenotypes for schizophrenia and suggests that endophenotypes are important measures to consider in characterizing the genetic basis of schizophrenia.

Author Affiliations: Department of Psychiatry (Drs Greenwood, Braff, Light, Cadenhead, Swerdlow, M. T. Tsuang, and Schork), Center for Human Genetics and Genomics (Drs Greenwood and Schork), and Department of Biostatistics (Dr Schork), University of California San Diego, La Jolla; Department of Psychiatry, University of Pennsylvania, Philadelphia (Drs Calkins, R. E. Gur, R. C. Gur, and Turetsky); Department of Psychiatry and Behavioral Sciences, University of Washington (Drs Dobie, Radant, and D. W. Tsuang), and VA Puget Sound Health Care System (Drs Dobie, Radant, and D. W. Tsuang), Seattle, Washington; Department of Psychiatry, University of Colorado Health Sciences Center, Denver (Drs Freedman and Olincy); Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine (Drs Green and Nuechterlein), and Neuropsychiatric Institute Biostatistics Core (Dr Mintz), University of California Los Angeles, Los Angeles; Massachusetts Mental Health Center, Public Psychiatry Division of the Beth Israel Deaconess Medical Center, and Department of Psychiatry, Harvard Medical School (Drs Seidman, Stone, and M. T. Tsuang), and Harvard Institute of Psychiatric Epidemiology and Genetics (Drs Seidman, Stone, and M. T. Tsuang), Boston, Massachusetts; and Department of Psychiatry, The Mount Sinai School of Medicine (Drs Siever and Silverman), James J. Peters VA Medical Center (Dr Siever), and Veterans Integrated Service Network 3 Mental Illness Research, Education and Clinical Center (Dr Siever), New York, NY.

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