, 2007) along with 35 additional family members, which had been genotyped after 2005. Overall, Study 2 sample consisted of 1,302 better genotyped subjects including (a) 485 subjects with all 25 markers (11 whole-genome scan markers, 14 fine-mapping markers) genotyped, (b) 794 subjects with 18 markers (4 whole-genome scan markers, 14 fine-mapping markers) genotyped, and (c) 23 subjects with data for 11 genome-wide scan markers only (i.e., sample included in the genome-wide scan but for whom the fine-mapping was unsuccessful). The multipoint and single-point linkage analyses were performed using program MERLIN (Abecasis et al., 2002). A nonparametric linkage analysis of DSM-IV ND affection status using Whittmore and Halpern (1994) NPL statistics to test for allele sharing among affected individuals was performed both within pairs (pairs) and arbitrary groups of individuals (all).
The continuous traits were analyzed using MERLIN regression-based linkage analysis estimating the IBD at 2-cM intervals. When significant/suggestive linkage signals were obtained, sex differences were studied by analyzing males and females separately. In addition, in Study 2 the regular smokers of the sample were divided into groups of current and former smokers, and these groups were analyzed separately. The linkage analysis results are expressed as LOD scores, and the most significant result of the trait, maximum LOD (MLOD) score, is presented. Results Study 1 The linkage analysis in the replication sample of 759 individuals yielded significant linkage with the DSM-IV phenotype on 20p11.
21 at marker D20S871, with MLOD score of 3.8 (single-point, ��pairs��; Figure 1). In sex-specific analyses (Figure 2), males provided suggestive evidence for linkage at marker D20S871 (20p11.21) with MLOD score of 2.6 (single-point, ��all��), whereas a significant linkage with MLOD score of 3.4 (single-point, all) was observed in females at marker D20S884 (20q11.23). No significant linkage was observed with either FTND or the lifetime MaxCigs24. Figure 1. Results of single-point and multipoint linkage analyses (testing for allele sharing within pairs of affected individuals) for the replication material (Study 1) on chromosome 20 for DSM-IV nicotine dependence diagnosis. Figure 2.
Result of single-point and multipoint linkage analyses (testing for allele sharing within arbitrary groups of affected individuals) for the males and females of the replication material (Study 1) on chromosome 20 for DSM-IV nicotine dependence diagnosis. … Study 2 The linkage analyses of DSM-IV ND phenotype in the combined sample provided suggestive evidence for linkage on 20p11 peaking at marker D20S912 with MLOD score of 2.3 (multipoint, pairs; Figure 3). Sex-specific analyses revealed that this signal was driven by females; the MLOD score was 1.3 in males (single-point, all, D20S899, 20q13) and 3.3 in Carfilzomib females (single-point, all, D20S884, 20q11; Figure 4).