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 |
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Authors: | 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;the GENEVA Consortium |
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Institution: | Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA. |
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Abstract: | 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 Fagerstr?m 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. |
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Keywords: | CHRNB3 genome‐wide association studies meta‐analysis phenotype definitions |
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