Bin B variants, located upstream of the coding region of CHRNA5, are associated with variability in CHRNA5 mRNA levels in European ancestry samples [Falvella, et al. 2010; Smith, et al. 2010; Wang, et al. 2009]. Low levels of CHRNA5 mRNA expression are associated with lower risk for nicotine dependence. No data exist on CHRNA5 mRNA expression in other populations, and further work to examine expression data and smoking behavior in other populations is needed. Because the risk allele of rs16969968 occurs primarily on the low mRNA expression alleles represented by bin B, conditional SNP analysis controlling for bin A (rs16969968) is important to distinguish between these two distinct mechanisms [Saccone, et al. 2010; Wang, et al. 2009]. This is an important example to demonstrate how a genetic effect could be better detected and characterized when additional related variants are taken into account.
