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加利福尼亚大学旧金山分校(UCSF)家族酗酒研究中的尼古丁依赖的连锁扫描。

Linkage scan of nicotine dependence in the University of California, San Francisco (UCSF) Family Alcoholism Study.

机构信息

Department of Genetics, University of North Carolina, Chapel Hill, NC 27599-7264, USA.

出版信息

Psychol Med. 2011 Apr;41(4):799-808. doi: 10.1017/S0033291710001273. Epub 2010 Jul 1.

Abstract

BACKGROUND

Nicotine dependence has been shown to represent a heritable condition, and several research groups have performed linkage analysis to identify genomic regions influencing this disorder though only a limited number of the findings have been replicated.

METHOD

In the present study, a genome-wide linkage scan for nicotine dependence was conducted in a community sample of 950 probands and 1204 relatives recruited through the University of California, San Francisco (UCSF) Family Alcoholism Study. A modified version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) with additional questions that probe nicotine use was used to derive DSM-IV nicotine dependence diagnoses.

RESULTS

A locus on chromosome 2q31.1 at 184 centiMorgans nearest to marker D2S2188 yielded a logarithm (base 10) of odds (LOD) score of 3.54 (point-wise empirical p=0.000012). Additional peaks of interest were identified on chromosomes 2q13, 4p15.33-31, 11q25 and 12p11.23-21. Follow-up analyses were conducted examining the contributions of individual nicotine dependence symptoms to the chromosome 2q31.1 linkage peak as well as examining the relationship of this chromosomal region to alcohol dependence.

CONCLUSIONS

The present report suggests that chromosome 2q31.1 confers risk to the development of nicotine dependence and that this region influences a broad range of nicotine dependence symptoms rather than a specific facet of the disorder. Further, the results show that this region is not linked to alcohol dependence in this population, and thus may influence nicotine dependence specifically.

摘要

背景

尼古丁依赖被证明是一种遗传性疾病,有几个研究小组进行了连锁分析,以确定影响这种疾病的基因组区域,但只有有限数量的发现得到了复制。

方法

本研究在加利福尼亚大学旧金山分校(UCSF)家庭酒精研究中通过 950 名个体和 1204 名亲属的社区样本进行了尼古丁依赖的全基因组连锁扫描。使用经过修改的酒精遗传学半结构评估(SSAGA),其中增加了探查尼古丁使用的问题,对 DSM-IV 尼古丁依赖进行诊断。

结果

在 2 号染色体 2q31.1 上距离标记 D2S2188 最近的 184 厘摩尔处的一个基因座产生了 3.54 的对数(以 10 为底)优势(LOD)评分(单点经验 P=0.000012)。还鉴定出染色体 2q13、4p15.33-31、11q25 和 12p11.23-21 上的其他感兴趣峰。进行了后续分析,检查了单个尼古丁依赖症状对 2q31.1 连锁峰的贡献,以及检查了该染色体区域与酒精依赖的关系。

结论

本报告表明 2 号染色体 2q31.1 赋予了尼古丁依赖发展的风险,并且该区域影响了广泛的尼古丁依赖症状,而不是该疾病的特定方面。此外,结果表明该区域与该人群中的酒精依赖不连锁,因此可能专门影响尼古丁依赖。

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