Browsing by Subject "Tobacco products"

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    CHRNB3 is more strongly associated with Fagerström test for cigarette dependence-based nicotine dependence than cigarettes per day: phenotype definition changes genome-wide association studies results
    (Wiley, 2012) Rice, John P.; Hartz, Sarah M.; Agrawal, Arpana; Almasy, Laura; Bennett, Siiri; Breslau, Naomi; Bucholz, Kathleen K.; Doheny, Kimberly F.; Edenberg, Howard J.; Goate, Alison M.; Hesselbrock, Victor; Howells, William B.; Johnson, Eric O.; Kramer, John; Krueger, Robert F.; Kuperman, Samuel; Laurie, Cathy; Manolio, Teri A.; Neuman, Rosalind J.; Nurnberger, John I.; Porjesz, Bernice; Pugh, Elizabeth; Ramos, Erin M.; Saccone, Nancy; Saccone, Scott; Schuckit, Marc; Bierut, Laura J.; GENEVA Consortium; Biochemistry and Molecular Biology, School of Medicine
    Aims: Nicotine dependence is a highly heritable disorder associated with severe medical morbidity and mortality. Recent meta-analyses have found novel genetic loci associated with cigarettes per day (CPD), a proxy for nicotine dependence. The aim of this paper is to evaluate the importance of phenotype definition (i.e., CPD versus Fagerström test for cigarette dependence (FTCD) score as a measure of nicotine dependence) on genome-wide association studies of nicotine dependence. Design: Genome-wide association study. Setting: Community sample. Participants: A total of 3365 subjects who had smoked at least one cigarette were selected from the Study of Addiction: Genetics and Environment (SAGE). Of the participants, 2267 were European Americans, 999 were African Americans. Measurements: Nicotine dependence defined by FTCD score ≥4, CPD. Findings: The genetic locus most strongly associated with nicotine dependence was rs1451240 on chromosome 8 in the region of CHRNB3 [odds ratio (OR) = 0.65, P = 2.4 × 10(-8) ]. This association was further strengthened in a meta-analysis with a previously published data set (combined P = 6.7 × 10(-16) , total n = 4200). When CPD was used as an alternate phenotype, the association no longer reached genome-wide significance (β = -0.08, P = 0.0004). Conclusions: Daily cigarette consumption and the Fagerstrom Test for Cigarette Dependence show different associations with polymorphisms in genetic loci.