The Use of Neurocognitive Endophenotypes in Large-Scale Family Genetic Studies of Schizophrenia

Abstract

Neurocognitive deficits are core features of schizophrenia and are among the most promising candidate endophenotypes for genetic studies of this disorder. The detection of gene-endophenotype associations requires large family cohort or case-control samples that are often only possible to collect through multisite collaborations, which presents considerable challenges for the use of endophenotypes. This chapter focuses on the rationale for using neurocognitive tasks of working memory, attention, and verbal declarative memory in large-scale, collaborative efforts to apply an endophenotype approach to schizophrenia. As an example, we describe the Consortium on the Genetics of Schizophrenia (COGS), a seven-site research network that investigates the genetic architecture of these neurocognitive and other candidate endopheno-types in families with schizophrenia. After providing a brief overview of the rigorous recruitment, data acquisition, and quality assurance procedures established by the COGS, we present recent results from this project that support utility of these procedures and the validity of neurocognitive endophenotypes. We conclude with a discussion of preliminary COGS findings that point toward specific candidate genes and future directions for this and other large-scale endophenotype studies of schizophrenia.