Endophenotypes successfully lead to gene identification: results from the collaborative study on the genetics of alcoholism.
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.
Dick
Danielle M
DM
Washington University School of Medicine, St. Louis, MO, USA. dickd@wustl.edu
Jones
Kevin
K
Saccone
Nancy
N
Hinrichs
Anthony
A
Wang
Jen C
JC
Goate
Alison
A
Bierut
Laura
L
Almasy
Laura
L
Schuckit
Marc
M
Hesselbrock
Victor
V
Tischfield
Jay
J
Foroud
Tatiana
T
Edenberg
Howard
H
Porjesz
Bernice
B
Begleiter
Henri
H
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