Among CHRNA6-CHRNB3 and CHRNA5-CHRNA3-CHRNB4 regions that have been widely associated to both alcohol and nicotine dependence before (Edenberg et al., 2004; Bierut et al., 2007; Saccone et al., 2007; Ray et al., 2009; Liu et al., 2010; Thorgeirsson et al., 2010), we only found that CHRNA6^rs6474421 was modestly associated with alcohol and nicotine co-dependence in the European-American discovery cohort (p=0.005). Furthermore, this modest association was not replicated in the Australian and African-American replication cohorts, nor did the marker make the top-ranked gene list in the present study, consistent with previous results using the same SAGE dataset (Bierut et al., 2010; Wang et al., 2011). Additionally, the risk genes identified by Lind et al. (2010) were not significantly associated with alcohol and nicotine co-dependence in our samples after Bonferroni correction. Critical difference between the study of Lind et al. (2010) and ours might result from the sample heterogeneity. Finally, in the present study, only the region between the TSS of IPO11 and the TSS of HTR1A was studied. The 5′ regulatory regions, which boundaries are hard to defined, of both genes were excluded. Some information in these 5′ regulatory regions might be lost.
