The neuronal nicotinic receptor subunit genes (CHRNA6 and CHRNB3) are associated with subjective responses to tobacco.
Neuronal nicotinic acetylcholine receptors have been implicated in various measures of nicotine dependence. In this paper, we present findings from an exploratory study of single nucleotide polymorphisms (SNPs) in the CHRNB3 and CHRNA6 genes with tobacco and alcohol phenotypes, including frequency of use and three subjective response factors occurring shortly after initiation of use. Subjects were 1056 ethnically diverse adolescents ascertained from clinical and community settings. The most significant associations were found between two CHRNB3 SNPs (rs4950 and rs13280604) and the three subjective response factors to initial tobacco use. These findings were replicated in a separate community sample of 1524 families participating in the National Longitudinal Study of Adolescent Health. Both CHRNB3 SNPs were found to be associated with similar measures of subjective response to tobacco. These results indicate that early subjective response to nicotine may be a valuable endophenotype for genetic studies aimed at uncovering genes contributing to nicotine use and addiction.
Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA.
Joanna S
JS
Zeiger
Brett C
BC
Haberstick
Isabel
I
Schlaepfer
Allan C
AC
Collins
Robin P
RP
Corley
Thomas J
TJ
Crowley
John K
JK
Hewitt
Christian J
CJ
Hopfer
Jeffrey
J
Lessem
Matthew B
MB
McQueen
Soo Hyun
SH
Rhee
Marissa A
MA
Ehringer
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data; D000437:Alcoholism / Q000235:genetics; D000483:Alleles; D003627:Data Interpretation, Statistical; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D014644:Genetic Variation; D006239:Haplotypes; D006630:Hispanic or Latino / Q000706:statistics & numerical data; D006801:Humans; D016014:Linear Models; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D035781:Siblings; D012907:Smoking / Q000235:genetics; D014029:Tobacco Use Disorder / Q000235:genetics*; D044465:White People / Q000706:statistics & numerical data
C470410:CHRNA6 protein, human; C447159:CHRNB4 protein, human; D005819:Genetic Markers; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic