In addition to rs16969968, several other variants in this gene cluster (e.g., rs680244, associated with gene expression) have been associated with smoking as well as alcohol use. Broadly speaking, the linkage disequilibrium (LD) patterns across the genes indicate the presence of 3-4 bins tagged by variants - rs3841324 (CHRNA5 promoter), rs16969968, and rs578776 (3′-UTR of CHRNA3) [56] and there is evidence that these LD bins vary in their relationships with smoking, across populations [57, 58], with each exerting putatively independent effects.
