To test this possibility, we assessed the association of SNPs in the CHRNB3-A6 locus with scores on WAIS tests of memory and cognitive function. Our analysis of the individuals in the COGA dataset suggests that one SNP, rs7017612, which lies in the intergenic region between CHRNB3 and CHRNA6, is associated with increased score on the WAIS Digit Symbol test. This test is thought to largely measure processing speed, but also, to some extent, memory. rs7017612 itself has not been reported to be associated with nicotine dependence. However, it is in moderately high LD (r2 = 0.75) with rs6474413, a SNP tagging the genome-wide significant bin for decreased risk for nicotine dependence. Thus, our data are consistent with the possibility that improved performance on this particular cognitive test is modestly associated with a decreased risk for nicotine dependence and that alleles of SNPs in these regions have effects on a subset of cognitive pathways best captured here by the WAIS digit symbol test. It is possible, however, that a function other than addiction or cognition is the true phenotype undergoing natural selection at these loci.
