This is the most comprehensive survey of the nicotinic receptor subunit genes for involvement in nicotine dependence to date. We have further explored the relationship between nicotine dependence and this gene family using 226 SNPs genotyped in the NICSNP sample of nicotine dependent cases and non-dependent smoking controls. Four distinct findings, two in the CHRNA5-CHRNA3-CHRNB4 cluster, one in CHRNB3-CHRNA6, and one in CHRND-CHRNG are significant after multiple test correction across the CHRN gene family. Additional genes CHRNA4 and CHRNB1 harbor nominally significant SNPs. Those CHRN genes that were not nominally associated in our initial reports (Bierut et al., 2007; Saccone et al., 2007a) still lack significant association with nicotine dependence with the denser SNP coverage.
