This study highlights variants in several nicotinic receptor subunit genes, besides CHRNA5-CHRNA3-CHRNB4 on chromosome 15q25, that affect the risk of developing nicotine dependence in our diverse sample of African-Americans and European-Americans. These include SNPs in or near CHRNG, CHRNA7, CHRNA10, CHRNA4, CHRNB1, and in the putative promoter region of CHRNB3-CHRNA6. In CHRNG and CHRNA4, the associated SNPs show differing effects in African-Americans and European Americans, while the other genes harbor SNPs that show some evidence for consistent effects in the two populations. In both populations, these additional nicotinic receptor loci substantially increase the explained trait variation. In the new African-American sample, no SNPs surpass Bonferroni-corrected significance for the 144 SNPs tested. However, in the full sample, combining African-Americans and both new and previously-reported European-Americans, the CHRNG SNP rs1881492 is significant with a 2-df test p-value of 4.25 × 10−5 and opposite directions of effect in the two populations. Strengths of the current study include the careful phenotyping of stringently defined nicotine-dependent cases and non-dependent smoking controls, and the inclusion of both European-ancestry and African-ancestry subjects.
