title: Endophenotypes successfully lead to gene identification: results from the collaborative study on the genetics of alcoholism.
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.
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA. dickd@wustl.edu
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Dick
authors.forename: Kevin
authors.initials: K
authors.lastname: Jones
authors.forename: Nancy
authors.initials: N
authors.lastname: Saccone
authors.forename: Anthony
authors.initials: A
authors.lastname: Hinrichs
authors.forename: Jen C
authors.initials: JC
authors.lastname: Wang
authors.forename: Alison
authors.initials: A
authors.lastname: Goate
authors.forename: Laura
authors.initials: L
authors.lastname: Bierut
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.forename: Marc
authors.initials: M
authors.lastname: Schuckit
authors.forename: Victor
authors.initials: V
authors.lastname: Hesselbrock
authors.forename: Jay
authors.initials: J
authors.lastname: Tischfield
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.forename: Howard
authors.initials: H
authors.lastname: Edenberg
authors.forename: Bernice
authors.initials: B
authors.lastname: Porjesz
authors.forename: Henri
authors.initials: H
authors.lastname: Begleiter
mesh_terms: D000437:Alcoholism / Q000235:genetics* / Q000503:physiopathology; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000648:ultrastructure; D002894:Chromosomes, Human, Pair 4; D002897:Chromosomes, Human, Pair 7; D004569:Electroencephalography; D005190:Family; D006801:Humans; D010641:Phenotype