Follow-up analyses of the chromosome 2 linkage peak showed that SSAGA symptoms encompassing a broad range of DSM-IV nicotine dependence symptom clusters, including evidence of tolerance, inability to quit smoking, escalating pattern of use, and persistent use despite negative health consequences, provided modest contributions to the linkage signal. This suggests the chromosome 2 locus at 184 cM confers risk for nicotine dependence in general rather than a specific facet of this disorder. As further evidence of this conclusion, it is notable that the linkage analysis of the nicotine dependence diagnosis yielded a higher LOD score than any of the individual nicotine dependence symptoms (LOD = 3.54 vs. max LOD = 2.66). These results are consistent with a previous study demonstrating that a single genetic factor can explain a predominant proportion of the common variation between DSM-IV nicotine dependence symptoms (Lessov et al., 2004).
