We performed selected multilocus analyses of case-control status. The purpose of these analyses is to help clarify and distinguish among the effects of multiple significant SNPs within an associated region but not in strong LD. The non-synonymous SNP rs16969968 in CHRNA5 is a biologically promising finding in our analysis, and other studies have shown evidence for replication via our analysis of rs16969968 in independent samples of families (Bierut et al., In press) and heavy smokers and controls (Stevens et al., unpublished data in review), and via analyses of strongly correlated SNPs by independent groups studying cigarettes-per-day (Berrettini et al., 2008) and cigarettes-per-day and nicotine dependence (Thorgeirsson et al., 2008). Furthermore, a new functional study has demonstrated that the risk allele at rs16969968 decreases response to a nicotine agonist (Bierut et al., In press). Therefore we targeted rs16969968 for these joint analyses; results for SNPs having high r2 with it will necessarily be similar.
