• Journal Article

CHRNB3 is more strongly associated with FTCD-based nicotine dependence than cigarettes per day: phenotype definition changes GWAS results

Citation

Rice, J. P., Hartz, S., Agrawal, A., Almasy, L., Bennett, S., Breslau, N., ... Bierut, L. J. (2012). CHRNB3 is more strongly associated with FTCD-based nicotine dependence than cigarettes per day: phenotype definition changes GWAS results. Addiction, 107(11), 2019-2028. DOI: 10.1111/j.1360-0443.2012.03922.x

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 Fagerstrom 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 3,365 subjects who had smoked at least one cigarette were selected from the Study of Addiction: Genetics and Environment (SAGE). Of the participants, 2,267 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 (OR=0.65, p=2.4x10(-8) ). This association was further strengthened in a meta-analysis with a previously published dataset (combined p=6.7 x10(-16) , total n=4,200). When CPD was used as an alternate phenotype, the association no longer reached genome-wide significance (beta=-0.08, p=0.0007). Conclusions: Daily cigarette consumption and the Fagerstrom Test for Cigarette Dependence (FTCD) show different associations with polymorphisms in genetic loci