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A systems biology network model for genetic association studies of nicotine addiction and treatment.一种用于尼古丁成瘾与治疗基因关联研究的系统生物学网络模型。
Pharmacogenet Genomics. 2009 Jul;19(7):538-51. doi: 10.1097/FPC.0b013e32832e2ced.
2
Dopamine genes and nicotine dependence in treatment-seeking and community smokers.寻求治疗的吸烟者和社区吸烟者中的多巴胺基因与尼古丁依赖
Neuropsychopharmacology. 2009 Sep;34(10):2252-64. doi: 10.1038/npp.2009.52. Epub 2009 Jun 3.
3
Nicotine withdrawal symptoms following a quit attempt: an ecological momentary assessment study among adolescents.戒烟尝试后的尼古丁戒断症状：一项针对青少年的生态瞬时评估研究
Nicotine Tob Res. 2009 Jun;11(6):722-9. doi: 10.1093/ntr/ntp055. Epub 2009 May 7.
4
Association of tobacco dependence and quit attempt duration with Rasch-modeled withdrawal sensitivity using retrospective measures.使用回顾性测量方法，研究烟草依赖和戒烟尝试持续时间与基于拉施模型的戒断敏感性之间的关联。
Addiction. 2009 Jun;104(6):1027-35. doi: 10.1111/j.1360-0443.2009.02540.x.
5
Genetic linkage findings for DSM-IV nicotine withdrawal in two populations.两个群体中与《精神疾病诊断与统计手册》第四版尼古丁戒断相关的基因连锁研究结果。
Am J Med Genet B Neuropsychiatr Genet. 2009 Oct 5;150B(7):950-9. doi: 10.1002/ajmg.b.30924.
6
Dopamine and opioid gene variants are associated with increased smoking reward and reinforcement owing to negative mood.多巴胺和阿片类基因变异与因负面情绪导致的吸烟奖赏和强化增加有关。
Behav Pharmacol. 2008 Sep;19(5-6):641-9. doi: 10.1097/FBP.0b013e32830c367c.
7
Nicotinic acetylcholine receptor beta2 subunit gene implicated in a systems-based candidate gene study of smoking cessation.烟碱型乙酰胆碱受体β2亚基基因与一项基于系统的戒烟候选基因研究有关。
Hum Mol Genet. 2008 Sep 15;17(18):2834-48. doi: 10.1093/hmg/ddn181. Epub 2008 Jul 1.
8
A searchable database of genetic evidence for psychiatric disorders.一个可搜索的精神疾病遗传证据数据库。
Am J Med Genet B Neuropsychiatr Genet. 2008 Sep 5;147B(6):671-5. doi: 10.1002/ajmg.b.30802.
9
Neurobiology of nicotine addiction: implications for smoking cessation treatment.尼古丁成瘾的神经生物学：对戒烟治疗的启示。
Am J Med. 2008 Apr;121(4 Suppl 1):S3-10. doi: 10.1016/j.amjmed.2008.01.015.
10
An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study.评估μ-阿片受体（OPRM1）作为纳曲酮治疗酒精依赖反应预测指标的研究：酒精依赖联合药物治疗与行为干预（COMBINE）研究结果
Arch Gen Psychiatry. 2008 Feb;65(2):135-44. doi: 10.1001/archpsyc.65.2.135.

尼古丁戒断敏感性、与 chr6q26 的连锁关系以及 OPRM1 SNPs 在家庭吸烟研究（SMOFAM）样本中的关联。

Nicotine withdrawal sensitivity, linkage to chr6q26, and association of OPRM1 SNPs in the SMOking in FAMilies (SMOFAM) sample.

机构信息

SRI International, Menlo Park, CA 94025, USA.

出版信息

Cancer Epidemiol Biomarkers Prev. 2009 Dec;18(12):3399-406. doi: 10.1158/1055-9965.EPI-09-0960.

DOI:10.1158/1055-9965.EPI-09-0960
PMID:19959688
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3536862/
Abstract

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 <0.05 and false discovery rate Q values <0.06.

CONCLUSION

An increased risk of relapse, suggestive linkage at chr6q26, and nominally significant association with multiple OPRM1 SNPs were found with Rasch-modeled nicotine withdrawal sensitivity scores in a multiplex smoking pedigree sample. Future studies should attempt to replicate these findings and investigate the relationship between nicotine withdrawal symptoms and variation at OPRM1.

摘要

背景

尼古丁戒断症状与戒烟有关。拉什模型已被用于开发代表尼古丁戒断的多个相关测量的一维敏感性评分。先前的常染色体全基因组筛查发现，9 种戒断症状总和的非参数连锁（NPL）对数似然比（LOD）评分在 6q26 染色体上为 2.7。

方法

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）对 158 个家系中的 432 个人进行常染色体全基因组 NPL 分析，这些家系具有微卫星基因型和尼古丁戒断评分，以及（c）在 172 个核家系中探索候选基因（OPRM1）中的单核苷酸多态性（SNP）与尼古丁戒断敏感性的基于家族的关联，这些家系有 419 个人具有 SNP 基因型和尼古丁戒断评分。

结果

与尼古丁戒断敏感性评分相关的复发风险增加（优势比，1.25；95%置信区间，1.10-1.42）。在 chr6q26 上鉴定出尼古丁戒断敏感性的最大 NPL LOD 评分 3.15，提示存在显著连锁。通过基于家族的关联检验，使用尼古丁戒断敏感性评分对 18 个 OPRM1 SNPs 进行评估，确定了 8 个具有全局 P 值 <0.05 和错误发现率 Q 值 <0.06 的标记 SNP。

结论

在一个多态吸烟家系样本中，使用拉什模型的尼古丁戒断敏感性评分发现，复发风险增加、chr6q26 处的提示性连锁以及与多个 OPRM1 SNPs 的名义显著关联。未来的研究应尝试复制这些发现，并研究尼古丁戒断症状与 OPRM1 变异之间的关系。