Effect of neuronal nicotinic acetylcholine receptor genes (CHRN) on longitudinal cigarettes per day in adolescents and young adults.
BACKGROUND
Few studies have sought to identify specific genetic markers associated with cigarettes per day (CPD) during adolescence and young adulthood, the period of greatest vulnerability for the development of nicotine dependence.


METHODS
We used a longitudinal design to investigate the effect of neuronal nicotinic acetylcholine receptor (CHRN) subunit genes on CPD from 15 to 21 years of age in young smokers of European descent (N = 439, 59% female). The number of CPD typically smoked during the previous 30 days was self-reported. Single nucleotide polymorphisms (SNPs) from CHRN genes were genotyped using DNA extracted from saliva samples collected at the 5-year assessment. Mixed-model analyses of SNP effects were computed across age at the time of assessment using log-transformed CPD as the phenotype. Data from the 1000 Genomes Project were used to clarify the architecture of CHRN genes to inform SNP selection and interpretation of results.


RESULTS
CPD was associated with a CHRNB3A6 region tagged by rs2304297, with CHRNA5A3B4 haplotype C (tagged by rs569207), and with the CHRNA2 SNP rs2271920, ps < .004. The reliability of single-SNP associations was supported by the correspondence between a more extensive set of SNP signals and the underlying genetic architecture. The 3 signals identified in this study appear to make independent contributions to CPD, and their combined effect accounts for 5.5% of the variance in log-transformed CPD.


CONCLUSIONS
Level of CPD during adolescence and young adulthood is associated with CHRNB3A6, CHRNA5A3B4, and CHRNA2.
Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT;
Dale S
DS
Cannon
Robin J
RJ
Mermelstein
Donald
D
Hedeker
Hilary
H
Coon
Edwin H
EH
Cook
William M
WM
McMahon
Cindy
C
Hamil
Diane
D
Dunn
Robert B
RB
Weiss
D000293:Adolescent; D002641:Chicago / Q000453:epidemiology; D015331:Cohort Studies; D004247:DNA / Q000032:analysis / Q000302:isolation & purification; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D016045:Human Genome Project; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D012463:Saliva / Q000737:chemistry; D012907:Smoking / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D011795:Surveys and Questionnaires; D014029:Tobacco Use Disorder / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D014505:Urban Population; D055815:Young Adult
D005819:Genetic Markers; D011978:Receptors, Nicotinic; D004247:DNA