, 2007). The former study reported 35 SNPs with suggestive evidence of association with nicotine dependence (p<.0001), found strong evidence for small effects being played by a number of cholinergic genes, and nominated Neurexin 1 and CHRNB3 as genes having a potentially critical role in nicotine dependence. The latter study identified more than 20 genes with significant Nilotinib Bcr-Abl inhibitor evidence of association with a substantial portion of those genes coding for nicotinic receptors. We attempted to confirm and extend the most significant of these findings into an epidemiologically sound population using the Iowa Adoption Studies, the largest case�Ccontrol adoption study of substance abuse in the United States (Cadoret, Troughton, O��Gorman, & Heywood, 1986; Cadoret, Yates, Troughton, Woodworth, & Stewart, 1995; Yates, Cadoret, & Troughton, 1998), for the most significantly associated SNPs from the NICSNP Consortium’s high-density association study and for every SNP from their genotyping of nicotinic receptors that were analyzed in the candidate gene analysis.

Methods The methods and procedures of the Iowa Adoption Studies have been described extensively elsewhere (Yates et al., 1998). All procedures described here were approved by the University of Iowa Institutional Review Board for Human Subjects. The behavioral data for this study were derived from interviews conducted during the past two waves of the study (1999�C2004 and 2004�Ccurrent) using an adapted version of the Semi-Structured Assessment for the Genetics of Alcoholism, Version II (Bucholz et al.

, 1994), a robust, widely used instrument that allows assessment of DSM-IV substance use dependence and a variety of other common behavioral illnesses. Using these data, we derived symptom counts for nicotine dependence (maximum score of 7) in this population using criteria from DSM-IV (American Psychiatric Association, 1994). Similarly, total scores for the Fagerstr?m Test for Nicotine Dependence (FTND) Scale (maximum score of 10; Heatherton, Kozlowski, Frecker, & Fagerstr?m, 1991) were determined using these data. The first set of SNPs (see Supplementary Table 1) contained 33 of the 35 most significantly associated SNP variants from the 2006 high-density association analysis (Bierut et al., 2007). The second set of SNPs (see Supplementary Table 1) contained 129 polymorphisms from 21 candidate genes for nicotine dependence, including 15 nicotinic genes, from the candidate gene (Saccone et al.

, 2007) and high-density association analyses. Genotyping for the present study was performed by Sequenom Inc. (San Diego, CA) using DNA prepared in our laboratory from whole blood using cold protein precipitation (Lahiri & Nurnberger, Entinostat 1991) or from lymphoblast DNA provided from the National Institutes of Health Rutgers Repository.