To identify susceptibility loci for nicotine dependence, more than 20 linkage analyses across the entire genome have been conducted using a family-based and/or sib-pair design (for a review, see 83). Although a number of genomic regions were identified as significant or suggestive for harboring susceptibility loci for nicotine dependence or smoking-related phenotypes, only four linkage regions have been replicated in four or more independent samples---these reside on human chromosomes 9q, 10q, 11p, and 17p (82). Recently a genome-wide linkage scan suggested that a region on human chromosome 2q31.1 confers risk for the development of nicotine dependence with a broad range of dependence symptoms rather than a specific aspect of the disorder (51).
