Association of the neuronal nicotinic receptor beta2 subunit gene (CHRNB2) with subjective responses to alcohol and nicotine.
Nicotine addiction and alcohol dependence are highly comorbid disorders that are likely to share overlapping genetic components. We have examined two neuronal nicotinic receptor subunit genes (CHRNA4 and CHRNB2) for possible associations with nicotine and alcohol phenotypes, including measures of frequency of use and measures of initial subjective response in the period shortly after first using the drugs. The subjects were 1,068 ethnically diverse young adults participating in ongoing longitudinal studies of adolescent drug behaviors at the University of Colorado, representing both clinical and community samples. Analysis of six SNPs in the CHRNA4 gene provided modest support for an association with past 6 month use of alcohol in Caucasians (three SNPs with P < 0.08), but no evidence for an association with tobacco and CHRNA4 was detected. However, a SNP (rs2072658) located immediately upstream of CHRNB2 was associated with the initial subjective response to both alcohol and tobacco. This study provides the first evidence for association between the CHRNB2 gene and nicotine- and alcohol-related phenotypes, and suggests that polymorphisms in CHRNB2 may be important in mediating early responses to nicotine and alcohol.
Ehringer
Marissa A
MA
Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado 80309, USA. Marissa.Ehringer@colorado.edu
Clegg
Hilary V
HV
Collins
Allan C
AC
Corley
Robin P
RP
Crowley
Thomas
T
Hewitt
John K
JK
Hopfer
Christian J
CJ
Krauter
Kenneth
K
Lessem
Jeffrey
J
Rhee
Soo Hyun
SH
Schlaepfer
Isabel
I
Smolen
Andrew
A
Stallings
Michael C
MC
Young
Susan E
SE
Zeiger
Joanna S
JS
D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics*; D019973:Alcohol-Related Disorders / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics; D003120:Colorado; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005163:Factor Analysis, Statistical; D005260:Female; D006239:Haplotypes; D006801:Humans; D007407:Interviews as Topic; D008137:Longitudinal Studies; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics*
D011978:Receptors, Nicotinic