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Chunk #0 — Introduction

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Association of CHRNA4 polymorphisms with smoking behavior in two populations.
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Cigarette smoking is the most preventable cause of mortality in the world. Despite increasing awareness of the risks associated with smoking, the World Health Organization (2002) estimated that around 1.2 billion people worldwide were active smokers. Nicotine contained in cigarettes is a rewarding drug and the primary substance responsible for continued smoking and addiction (Benowitz 2008). Thus, an understanding of the various factors that influence the risk of nicotine dependence (ND) is critical to the prevention and cessation of smoking. Although the etiology of ND is complex, a genetic contribution to ND has been well established from twin studies. The heritability was estimated to be 0.56 for all smokers on average in a meta-analysis of 17 twin studies (Li et al., 2003). Numerous ND candidate loci or genes have been identified by genome-wide linkage studies (for review see Li et al., 2008), candidate gene association studies (Gelernter et al., 2006; Saccone et al., 2007; Conti et al., 2008; Weiss et al., 2008; Bergen et al., 2009; Saccone et al., 2009a,b) and recent genome-wide association studies (GWAS) (Berrettini et al., 2008;