A genomic scan for habitual smoking in families of alcoholics: Common and specific genetic factors in substance dependence
A genomic scan for habitual smoking in families of alcoholics: Common and specific genetic factors in substance dependence
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DOI：
10.1002/ajmg.a.20329
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发表时间：
2004-01-01
影响因子：
2
通讯作者：
Reich, T
中科院分区：
文献类型：
--
作者：
Bierut, LJ;Rice, JP;Reich, T
吸烟是一种高度遗传的成瘾性疾病，通常与酒精依赖同时发生。本研究的目的是进行基因组筛选的习惯性吸烟和共病的习惯性吸烟和酒精依赖的家庭从酒精中毒的遗传学合作研究（COGA）。使用酒精中毒遗传学半结构化评估（SSAGA）对受试者进行评估，以评估酒精依赖和习惯性吸烟（每天吸烟一包或更多，持续至少6个月）。67个多代家庭，154个独立的兄弟姐妹对习惯性吸烟的影响进行了基因分型的筛选样本。对79个多代同堂家庭的173对兄弟姐妹进行了重复分析。使用ASPEX进行同胞对分析。筛选样本中的四个染色体区域在习惯性吸烟的兄弟姐妹对中具有增加的等位基因共享，LOD评分大于1（染色体5、9、11和21）。LOD值最高的是9号染色体（LOD=2.02;等位基因共享58.9%）。四个染色体区域也有适度的证据表明与习惯性吸烟和酒精依赖共病表型（染色体1，2，11，15）的连锁;最强的发现是在染色体2（LOD=3.30;等位基因共享69.1%）。先前确定的区域（染色体I和7）在同一数据集中与酒精依赖的发展有关，但在筛选样本中没有提供与习惯性吸烟相关的证据。在复制数据集中，在2号和9号染色体上的筛选样品中鉴定的峰附近等位基因共享继续增加，但结果是适度的。7号染色体上的一个区域，距离先前在与酒精依赖的连锁分析中确定的位置约60 cM，增加了共病习惯性吸烟和酒精依赖的等位基因共享。这些数据提供的证据表明，特定的遗传区域参与了习惯性吸烟而不是酒精依赖的发展。相反，影响酒精依赖发展的遗传区域似乎并不有助于习惯性吸烟的发展。最后，也有证据表明，2号染色体上的一个区域可能反映了习惯性吸烟和酒精依赖的共同遗传易感性位点。(C)2003 Wiley-Liss，Inc.
Smoking is a highly heritable, addictive disorder that commonly co-occurs with alcohol dependence. The purpose of this study is to perform a genomic screen for habitual smoking and comorbid habitual smoking and alcohol dependence in families from the Collaborative Study on the Genetics of Alcoholism (COGA). Subjects were assessed using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) to evaluate alcohol dependence and habitual smoking (smoking one pack per day or more for at least 6 months). Sixty seven multi-generational families with 154 independent sibling pairs affected with habitual smoking were genotyped in a screening sample. Analyses on 79 multi-generational families with 173 independent sibling pairs were repeated in a replication sample. Sibpair analyses were performed using ASPEX. Four chromosomal regions in the screening sample had increased allele sharing among sibling pairs for habitual smoking with a LOD score greater than 1 (chromosomes 5, 9, 11, and 21). The highest LOD score was on chromosome 9 (LOD=2.02; allele sharing 58.9%). Four chromosomal regions also had modest evidence for linkage to the comorbid phenotype habitual smoking and alcohol dependence (chromosomes 1, 2, 11, 15); and the strongest finding was on chromosome 2 (LOD=3.30; allele sharing 69.1%). Previously identified areas (chromosomes I and 7) implicated in the development of alcohol dependence in this same data set did not provide evidence for linkage to habitual smoking in the screening sample. In the replication data set, there continued to be increased allele sharing near peaks identified in the screening sample on chromosomes 2 and 9, but the results were modest. An area on chromosome 7, approximately 60 cM from a location previously identified in linkage analysis with alcohol dependence, had increased allele sharing for the comorbid habitual smoking and alcohol dependence. These data provide evidence of specific genetic regions involved in the development of habitual smoking and not alcohol dependence. Conversely, genetic regions that influence the development of alcohol dependence do not appear to contribute to the development of habitual smoking. Finally, there is also evidence of an area on chromosome 2 that may reflect a common genetic vulnerability locus to both habitual smoking and alcohol dependence. (C) 2003 Wiley-Liss, Inc.