The role of GABRA2 in risk for conduct disorder and alcohol and drug dependence across developmental stages.
We use findings from the behavior genetics literature about how genetic factors (latently) influence alcohol dependence and related disorders to develop and test hypotheses about the risk associated with a specific gene, GABRA2, across different developmental stages. This gene has previously been associated with adult alcohol dependence in the Collaborative Study of the Genetics of Alcoholism (COGA) sample [Edenberg, H. J., Dick, D. M., Xuei, X., Tian, H., Almasy, L., Bauer, L. O., Crowe, R., Goate, A., Hesselbrock, V., Jones, K. A., Kwon, J., Li, T. K., Nurnberger Jr., J. I., O'Connor, S. J., Reich, T., Rice, J., Schuckit, M., Porjesz, B., Foroud, T., and Begleiter, H. (2004). Am. J. Hum. Genet. 74:705-714] and other studies [Covault, J., Gelernter, J., Hesselbrock, V., Nellissery, M., and Kranzler, H. R. (2004). Am. J. Med. Genet. B Neuropsychiatr. Genet. 129B:104-109; Lappalainen, J., Krupitsky, E., Remizov, M., Pchelina, S., Taraskina, A., Zvartau, E., Somberg, L. K., Covault, J., Kranzler, H. R., Krystal, J., and Gelernter, J. (2005). Alcohol. Clin. Exp. Res. 29:493-498]. In a sample of children and adolescents ascertained as part of the COGA project, we find that GABRA2 is significantly associated with childhood conduct disorder symptoms, but not with childhood alcohol dependence symptoms. A consistent elevation in risk for alcohol dependence associated with GABRA2 is not evident until the mid-20s and then remains throughout adulthood. GABRA2 is also associated with other drug dependence in our sample, both in adolescence and adulthood.
Dick
Danielle M
DM
Department of Psychiatry and Psychology, Washington University School of Medicine, St. Louis, MO 63110, USA. dickd@wustl.edu
Bierut
Laura
L
Hinrichs
Anthony
A
Fox
Louis
L
Bucholz
Kathleen K
KK
Kramer
John
J
Kuperman
Samuel
S
Hesselbrock
Victor
V
Schuckit
Marc
M
Almasy
Laura
L
Tischfield
Jay
J
Porjesz
Bernice
B
Begleiter
Henri
H
Nurnberger
John
J
Xuei
Xiaoling
X
Edenberg
Howard J
HJ
Foroud
Tatiana
T
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000375:Aging / Q000502:physiology*; D000437:Alcoholism / Q000235:genetics* / Q000401:mortality; D002648:Child; D006801:Humans; D001523:Mental Disorders / Q000235:genetics* / Q000401:mortality; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000235:genetics*; D012044:Regression Analysis; D012307:Risk Factors; D019966:Substance-Related Disorders / Q000235:genetics* / Q000401:mortality; D016019:Survival Analysis; D014481:United States
C484841:GABRA2 protein, human; D011963:Receptors, GABA-A