Li Ming D
Department of Psychiatry and Neurobehavioral Sciences, Section of Neurobiology, University of Virginia, 1670 Discovery Drive, Suite 110, Charlottesville, VA 22911, USA.
Hum Genet. 2008 Mar;123(2):119-31. doi: 10.1007/s00439-008-0473-0. Epub 2008 Jan 19.
Tobacco smoking is a severe health hazard worldwide, as nearly one-third of the global adult population smokes tobacco products. This high prevalence highlights the importance of studying the genetic determinants of nicotine dependence (ND). To identify such genetic factors, more than 20 genome-wide linkage studies have been conducted across different populations using a variety of ND assessment approaches, including smoking quantity (SQ), Heaviness of Smoking Index (HSI), Fagerström Test for Nicotine Dependence (FTND), ever-smoking, habitual smoking, or maximum number of cigarettes smoked in a 24-h period. This review provides a critical update on the progress during the years since our last review, published in 2004, in identifying susceptibility loci for ND. Although a significant number of reported genomic regions did not reach the level of "suggestive" or "significant" linkage and failed to be replicated in other independent studies, thirteen regions, located on chromosomes 3-7, 9-11, 17, 20, and 22, have been found to be suggestive or significant in at least two independent samples. Among them, the regions on chromosomes 9 (91.9-136.5 cM), 10, 11, and 17 have received the strongest support. A summary of eight regions that have been nominated for "significant" linkage to ND is provided.
吸烟在全球范围内对健康构成严重危害，因为全球近三分之一的成年人口吸烟。这种高流行率凸显了研究尼古丁依赖（ND）遗传决定因素的重要性。为了确定这些遗传因素，已经在不同人群中进行了20多项全基因组连锁研究，采用了多种ND评估方法，包括吸烟量（SQ）、吸烟严重程度指数（HSI）、尼古丁依赖Fagerström测试（FTND）、曾经吸烟、习惯性吸烟或24小时内吸烟的最大数量。本综述对自我们上次于2004年发表的综述以来，在确定ND易感基因座方面取得的进展进行了重要更新。尽管大量报告的基因组区域未达到“提示性”或“显著性”连锁水平，且未能在其他独立研究中得到重复验证，但位于3-7号、9-11号、17号、20号和22号染色体上的13个区域，已在至少两个独立样本中被发现具有提示性或显著性。其中，9号染色体（91.9-136.5 cM）、10号、11号和17号染色体上的区域得到了最强有力的支持。本文提供了八个被提名与ND存在“显著性”连锁的区域的总结。
