Identifying susceptibility loci for nicotine dependence: 2008 update based on recent genome-wide linkage analyses

Tobacco smoking is a severe health hazard worldwide, as nearly one-third of the global adult population smokes tobacco products. This high prevalence highlights the importance of studying the genetic determinants of nicotine dependence (ND). To identify such genetic factors, more than 20 genome-wide linkage studies have been conducted across different populations using a variety of ND assessment approaches, including smoking quantity (SQ), Heaviness of Smoking Index (HSI), Fagerström Test for Nicotine Dependence (FTND), ever-smoking, habitual smoking, or maximum number of cigarettes smoked in a 24-h period. This review provides a critical update on the progress during the years since our last review, published in 2004, in identifying susceptibility loci for ND. Although a significant number of reported genomic regions did not reach the level of "suggestive" or "significant" linkage and failed to be replicated in other independent studies, thirteen regions, located on chromosomes 3-7, 9-11, 17, 20, and 22, have been found to be suggestive or significant in at least two independent samples. Among them, the regions on chromosomes 9 (91.9-136.5 cM), 10, 11, and 17 have received the strongest support. A summary of eight regions that have been nominated for "significant" linkage to ND is provided.