Nicotine Withdrawal Sensitivity, Linkage to chr6q26, and Association of OPRM1 SNPs in the SMOking in FAMilies (SMOFAM) Sample
Nicotine Withdrawal Sensitivity, Linkage to chr6q26, and Association of OPRM1 SNPs in the SMOking in FAMilies (SMOFAM) Sample
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DOI：
10.1158/1055-9965.epi-09-0960
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发表时间：
2009-12-01
影响因子：
3.8
通讯作者：
Bergen, Andrew W.
中科院分区：
文献类型：
--
作者：
Hardin, Jill;He, Yungang;Bergen, Andrew W.
背景：尼古丁戒断症状与戒烟有关。Rasch模型已被用于开发代表尼古丁戒断多个相关指标的一维敏感性评分。先前的常染色体范围筛选确定了染色体6 q26上9种戒断症状之和的非参数连锁（NPL）对数似然比（LOD）评分为2.7。这些分析的目的是（a）评估尼古丁戒断敏感性对复发的影响，（B）在具有微卫星基因型和尼古丁戒断评分的432个个体的158个家系中进行尼古丁戒断敏感性的常染色体范围的NPL分析，以及（c）在172个核心家系中探索μ阿片受体候选基因（OPRM 1）处的单核苷酸多态性（SNP）与尼古丁戒断敏感性的基于家族的关联，其中419个个体具有SNP基因型和尼古丁戒断评分。复发风险增加与尼古丁戒断敏感性评分相关（比值比，1.25; 95%置信区间，1.10-1.42）。尼古丁戒断敏感性的最大NPL LOD评分为3.15，表明在chr 6 q26处存在显著连锁。通过以家族为基础的关联性检验与尼古丁戒断敏感性评分对18个OPRM 1 SNP进行评估，确定了8个具有全局P值的标签SNP
Background: Nicotine withdrawal symptoms are related to smoking cessation. A Rasch model has been used to develop a unidimensional sensitivity score representing multiple correlated measures of nicotine withdrawal. A previous autosome-wide screen identified a nonparametric linkage (NPL) log-likelihood ratio (LOD) score of 2.7 on chromosome 6q26 for the sum of nine withdrawal symptoms.Methods: The objectives of these analyses were to (a) assess the influence of nicotine withdrawal sensitivity on relapse, (b) conduct autosome-wide NPL analysis of nicotine withdrawal sensitivity among 158 pedigrees with 432 individuals with microsatellite genotypes and nicotine withdrawal scores, and (c) explore family-based association of single nucleotide polymorphism (SNP) at the mu opioid receptor candidate gene (OPRM1) with nicotine withdrawal sensitivity in 172 nuclear pedigrees with 419 individuals with both SNP genotypes and nicotine withdrawal scores.Results: An increased risk for relapse was associated with nicotine withdrawal sensitivity score (odds ratio, 1.25; 95% confidence interval, 1.10-1.42). A maximal NPL LOD score of 3.15, suggestive of significant linkage, was identified at chr6q26 for nicotine withdrawal sensitivity. Evaluation of 18 OPRM1 SNPs via the family-based association test with the nicotine withdrawal sensitivity score identified eight tagging SNPs with global P values