The chromosome 15q25 region containing CHRNA5-CHRNA3-CHRNB4 has been consistently associated with nicotine dependence and smoking in multiple studies (reviewed in (Greenbaum & Lerer, 2009)) and is clearly important. Evidence indicates there are multiple associated loci in this region that have low correlation with each other and may have distinct biological effects on risk. In European populations these distinct loci are represented by rs16969968 (a non-synonymous SNP in CHRNA5), rs578776 and rs588765. The association between rs16969968 and nicotine dependence has now been replicated in African-Americans. The results reported here now highlight additional nicotinic receptor genes as involved in nicotine dependence risk. However, none of these other CHRN genes show as much consistency in association across populations as rs16969968 and some of its correlates in CHRNA5-CHRNA3-CHRNB4. This suggests that these other CHRN genes need more investigation, and yet may be in a second “tier” of effects compared to the effects of variants on chromosome 15q25.
