The association of genetic risk factors with nicotine dependence may be influenced by characteristics of smoking behavior such as the number of quit attempts, smoking frequency in adolescents, and age at onset (AAO) of daily smoking [19], [20]. A study using haplotype analysis with variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster reported that variation in this cluster is associated with severity of nicotine dependence among long-term smokers who began daily smoking at age 16 or younger. Notably, this association was not present among those who began daily smoking after age 16 [21]. To further examine the impact of this gene cluster on the development of nicotine use, we tested whether variants within and flanking the CHRNA5-CHRNA3-CHRNB4 gene cluster affect AAO of daily smoking in a sample of adolescents and young adults from the COGA (Collaborative Study of the Genetics of Alcoholism) families.
