The two findings – one at rs16969968 and one at expression-associated SNPs such as rs588765 - have the appealing property of being at least LD proxies for functional effects [11, 33, 34], if not the functional SNPs themselves. It is plausible that these SNPs are responsible for two biological mechanisms affecting nicotine dependence risk: a coding change at CHRNA5 to asparagine (regardless of mRNA level) at rs16969968, and altered brain mRNA expression of the common (aspartate) form of CHRNA5, tagged by rs588765.
