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 < or = .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.
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 < or = .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.
Authors: Allen D Radant; Dorcas J Dobie; Monica E Calkins; Ann Olincy; David L Braff; Kristin S Cadenhead; Robert Freedman; Michael F Green; Tiffany A Greenwood; Raquel E Gur; Ruben C Gur; Gregory A Light; Sean P Meichle; Steve P Millard; Jim Mintz; Keith H Nuechterlein; Nicholas J Schork; Larry J Seidman; Larry J Siever; Jeremy M Silverman; William S Stone; Neal R Swerdlow; Ming T Tsuang; Bruce I Turetsky; Debby W Tsuang Journal: Psychophysiology Date: 2010-04-05 Impact factor: 4.016
Authors: Axel Krug; Valentin Markov; Sören Krach; Andreas Jansen; Klaus Zerres; Thomas Eggermann; Tony Stöcker; N Jon Shah; Markus M Nöthen; Alexander Georgi; Jana Strohmaier; Marcella Rietschel; Tilo Kircher Journal: Hum Brain Mapp Date: 2011-01 Impact factor: 5.038
Authors: Gregory A Light; Lisa E Williams; Falk Minow; Joyce Sprock; Anthony Rissling; Richard Sharp; Neal R Swerdlow; David L Braff Journal: Curr Protoc Neurosci Date: 2010-07
Authors: Michael S McCloskey; Antonia S New; Larry J Siever; Marianne Goodman; Harold W Koenigsberg; Janine D Flory; Emil F Coccaro Journal: J Psychiatr Res Date: 2009-02-18 Impact factor: 4.791
Authors: William S Stone; Raquelle I Mesholam-Gately; David L Braff; Monica E Calkins; Robert Freedman; Michael F Green; Tiffany A Greenwood; Raquel E Gur; Ruben C Gur; Laura C Lazzeroni; Gregory A Light; Keith H Nuechterlein; Ann Olincy; Allen D Radant; Larry J Siever; Jeremy M Silverman; Joyce Sprock; Catherine A Sugar; Neal R Swerdlow; Debby W Tsuang; Ming T Tsuang; Bruce I Turetsky; Larry J Seidman Journal: Schizophr Res Date: 2014-12-12 Impact factor: 4.939