associations with outcome. For instance, rs1229984 in alcohol dehydrogenase (ADH1B) gene was one of the earliest candidate gene variants proposed in the etiology of alcoholism, particularly in Asians (A Agrawal & Bierut, 2012)5. The variant, which is rather rare in European-American populations, has recently been identified in adequately powered genome-wide association studies as well (Bierut et al., 2012). Similarly, early candidate gene and experimental studies implicated a SNP in a nicotinic receptor (rs16969968 in CHRNA5) as a risk factor for tobacco smoking and nicotine dependence, but the role of this variant in cigarette smoking was not widely accepted until it was identified in multiple meta-analyses of cigarettes smoked per day, the largest of which had a sample size exceeding 70,000 (J. Z. Liu et al., 2010; Thorgeirsson et al., 2010; Tobacco_and_Genetics_Consortium, 2010).
