Similar to our results (Table 1), Haller et al. (2012) found few novel mis-sense variants in CHRNA5 that were more prevalent in the nicotine dependent (FTND≥4) than non-dependent (FTND≤1) African-American Collaborative Genetic Study of Nicotine Dependence sample (N=352). Likewise, whereas the NHLBI_ESP identified both known common and novel rare mis-sense CHRNA5 variants in African-Americans, the rare variants were extremely uncommon (MAF«1%). Two exceptions – rs2229961:G>A (V134I) and rs76766434:C>T (R401C) – occurred at slightly higher frequencies, but still had MAF<1% (Exome Variant Server, 2012). We identified 2 individuals in our heavy smoker population that were heterozygous at rs2229961:G>A, but did not find heterozygosity at rs76766434:C>T in any sequenced individual (Table 1). Haller et al. (2012) identified SNPs in CHRNB4 (rs12914008:A>G and rs61737499:G>A) and in CHRNA3 (rs8192475:C>T) that decreased risk for nicotine dependence in both Europeans and African-Americans, but did not find association of rare variants in CHRNB3, CHRNA6 or CHRNA5 with nicotine dependence in either population. Therefore, additional common or rare variants in CHRNA5 were not found in our African-American heavy smoker population likely because SNPs in other cholinergic receptor subunits
