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Schizophrenia Bulletin Advance Access published online on October 11, 2006
Schizophrenia Bulletin, doi:10.1093/schbul/sbl044
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© The Author 2006. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Gene/Phene Relationship

The Consortium on the Genetics of Endophenotypes in Schizophrenia: Model Recruitment, Assessment, and Endophenotyping Methods for a Multisite Collaboration

Monica E. Calkins 1 *, Dorcas J. Dobie 2, Kristin S. Cadenhead 3, Ann Olincy 4, Robert Freedman 4, Michael F. Green 5, Tiffany A. Greenwood 3, Raquel E. Gur 1, Ruben C. Gur 1, Gregory A. Light 3, Jim Mintz 6, Keith H. Nuechterlein 6, Allen D. Radant 2, Nicholas J. Schork 3, Larry J. Seidman 7, Larry J. Siever 8, Jeremy M. Silverman 9, William S. Stone 7, Neal R. Swerdlow 3, Debby W. Tsuang 2, Ming T. Tsuang 10, Bruce I. Turetsky 1, and David L. Braff 3
1 Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania, 10 Gates, 3400 Spruce St, Philadelphia, PA 19104
2 Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA; VA Puget Sound Health Care System, Seattle, WA
3 Department of Psychiatry, University of California San Diego, San Diego, CA
4 Department of Psychiatry, University of Colorado Health Sciences Center, Denver, CO
5 Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA; VA Greater Los Angeles Healthcare System
6 Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA
7 Department of Psychiatry, Harvard Medical School, Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston, MA; Harvard Institute of Psychiatric Epidemiology and Genetics, Boston, MA
8 Department of Psychiatry, The Mount Sinai School of Medicine, New York, NY; James J. Peters VA Medical Center and VISN3, Mental Illness Research Education and Clinical Center's (MIRECC)
9 Department of Psychiatry, The Mount Sinai School of Medicine, New York, NY
10 Department of Psychiatry, University of California San Diego, San Diego, CA; Department of Psychiatry, Harvard Medical School, Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston, MA; Harvard Institute of Psychiatric Epidemiology and Genetics, Boston, MA

* To whom correspondence should be addressed.
Monica E. Calkins, E-mail: mcalkins{at}bbl.med.upenn.edu


  Abstract

Background: The Consortium on the Genetics of Schizophrenia (COGS) is an ongoing, National Institute of Mental Health-funded, 7-site collaboration investigating the occurrence and genetic architecture of quantitative endophenotypes related to schizophrenia. The purpose of this article is to provide a description of the COGS structure and methods, including participant recruitment and assessment. Methods: The hypothesis-driven recruitment strategy ascertains families that include a proband with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia, and at least one unaffected full sibling available for genotyping and endophenotyping, along with parents available for genotyping and (optional depending on age) endophenotyping. The family structure is selected to provide contrast in quantitative endophenotypic traits and thus to maximize the power of the planned genetic analyses. Probands are recruited from many sources including clinician referrals, local National Alliance for the Mentally Ill chapters, and advertising via the media. All participants undergo a standardized protocol that includes clinical characterization, a blood draw for genotyping, and endophenotype assessments (P50 suppression, prepulse inhibition, antisaccade performance, continuous performance tasks, letter-number span, verbal memory, and a computerized neurocognitive battery). Investigators participate in weekly teleconferences to coordinate and evaluate recruitment, clinical assessment, endophenotyping, and continuous quality control of data gathering and analyses. Data integrity is maintained through use of a highly quality-assured, centralized web-based database. Results: As of February 2006, 355 families have been enrolled and 688 participants have been endophenotyped, including schizophrenia probands (n = 154, M:F = 110:44), first-degree biological relatives (n = 343, M:F = 151:192), and community comparison subjects (n = 191, M:F = 81:110). Discussion: Successful multisite genetics collaborations must institute standardized methodological criteria for assessment and recruitment that are clearly defined, well communicated, and uniformly applied. In parallel, studies utilizing endophenotypes require strict adherence to criteria for cross-site data acquisition, equipment calibration and testing and software equivalence, and continuous quality assurance for many measures obtained across sites. This report describes methods and presents the structure of the COGS as a model of multisite endophenotype genetic studies. It also provides demographic information after the first 2 years of data collection on a sample for whom the behavioral data and genetics of endophenotype performance will be fully characterized in future articles. Some issues discussed in the reviews that follow reflect the challenges of evaluating endophenotypes in studies of the genetic architecture of endophenotypes in schizophrenia.

Keywords: neurophysiology; neurocognitive; genes.
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