correlated variants are only weakly correlated with the D398N variant. The N398 variant, which greatly increases risk for nicotine dependence, occurs primarily on the background of low mRNA expression of CHRNA5. The nonrisk variant D398 occurs on both high- and low-expression alleles. The risk for nicotine dependence is significantly lower when D398 occurs on a background of low CHRNA5 mRNA expression than when it occurs on a background of high CHRNA5 mRNA expression (139).
