期刊
ADDICTION
卷 107, 期 11, 页码 2019-2028出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1360-0443.2012.03922.x
关键词
CHRNB3; genome-wide association studies; meta-analysis; phenotype definitions
资金
- NIH Genes, Environment and Health Initiative (GEI) [U01 HG004422]
- NIH GEI [U01HG004438]
- National Institute on Alcohol Abuse and Alcoholism
- National Institute on Drug Abuse
- NIH [HHSN268200782096C, K02DA021237, UL1RR024992, KL2RR024994, T32MH014677]
- NIH from the National Cancer Institute [P01 CA089392]
- NIDA [HHSN271200477451C]
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 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 X 10-8]. This association was further strengthened in a meta-analysis with a previously published data set (combined P?=?6.7 x 10-16, total n?=?4200). When CPD was used as an alternate phenotype, the association no longer reached genome-wide significance (beta?=?-0.08, P?=?0.0004). Conclusions Daily cigarette consumption and the Fagerstrom Test for Cigarette Dependence show different associations with polymorphisms in genetic loci.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据