This meta-analysis was designed to examine the relationship of SNPs in the CHRNA5/CHRNA3/CHRNB4 gene cluster with early smoking behaviors including AOI and AOS. Genetic variation in this genomic region shows robust association to nicotine dependence and tobacco use behaviors in adult samples [Furberg et al., 2010; Liu et al., 2010; Saccone et al., 2010a; Thorgeirsson et al., 2010]. Although previous studies examining association with tobacco initiation [Furberg et al., 2010; Thorgeirsson et al., 2010] and first regular use have been inconclusive, most have not found association with the locus including SNP rs16969968 [Furberg et al., 2010; Hartz et al., 2012; Thorgeirsson et al., 2010]. We hypothesized that a possible explanation for conflicting reports may be related to the multiple independent loci in this region [Saccone et al., 2009a; Saccone et al., 2010b], if different loci contribute to different smoking-related phenotypes. This analysis expands on previous work by examining two additional SNPs (rs1948 and rs684513) based on previous associations with smoking-related phenotypes [Amos et al., 2010; Schlaepfer et al., 2008; Winterer et al., 2010], in addition to three statistically independent nicotine dependence loci in the CHRNA5/A3/B4 gene cluster: rs16969968, rs578776, and rs588765.
