First, rs16969968, which causes an amino acid change in CHRNA5 and is clearly implicated in risk for nicotine dependence and lung cancer in individuals of European descent, is also significantly associated with nicotine dependence in African-Americans. This SNP is the most important one to test first: it is highly replicated, and in vitro studies demonstrate that α4β2α5 nicotinic receptors with the risk variant at rs16969968 exhibit lower maximal response to a nicotinic agonist than receptors with the other allele [11].
