Endophenotypes successfully lead to gene identification: Results from the collaborative study on the genetics of alcoholism

Danielle M. Dick, Kevin Jones, Nancy Saccone, Anthony Hinrichs, Jen C. Wang, Alison Goate, Laura Bierut, Laura Almasy, Marc Schuckit, Victor Hesselbrock, Jay Tischfield, Tatiana Foroud, Howard Edenberg, Bernice Porjesz, Henri Begleiter

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

The use of endophenotypes has been proposed as a strategy to aid gene identification efforts for complex phenotypes [Gottesman, I. I., and Shields J. (1972). Schizophrenia and Genetics: A Twin Study Vantage Point. London: Academic]. As part of the Collaborative Study of the Genetics of Alcoholism (COGA) project, we have analyzed electrophysiological endophenotypes, in addition to clinical diagnoses, as part of our effort to identify genes involved in the predisposition to alcohol dependence. In this paper we summarize published results from linkage and association analyses of two chromosomal regions in which the use of endophenotypes has successfully led to the identification of genes associated with alcohol dependence [GABRA2 (Edenberg et al., (2004). Am. J. Hum. Genet. 74:705-714) and CHRM2 (Wang et al., (2004). Hum. Mol. Genet. 13:1903-1911)]. Our experience in the COGA project has been that the analysis of endophenotypes provides several advantages over diagnostic phenotypes, including the strength and localization of the linkage signal. Our results provide an illustration of the successful use of endophenotypes to identify genes involved in the predisposition to a complex psychiatric phenotype, a strategy originally proposed by Gottesman and Shields in 1972.

Original languageEnglish
Pages (from-to)112-126
Number of pages15
JournalBehavior genetics
Volume36
Issue number1
DOIs
StatePublished - Jan 2006

Keywords

  • Alcohol dependence
  • Association
  • EEG
  • Endophenotype
  • Genetics
  • Linkage

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