functional variants associated with rs1044294 that differ between our samples. There is evidence that CHRN SNPs show opposite allelic effects with different drugs (Grucza et al. 2008; Sherva et al. 2010; Wang et al. 2008) and in some cases the major allele in EA samples is the minor allele in African American samples, so this is another factor that may contribute to directional differences in effect. Both rs1044394 and rs1044396 are synonymous mutations located in the 5th exon of CHRNA4. However, possible functional effects of these alleles remain unknown.