Dissection of the Phenotypic and Genotypic Associations With Nicotinic Dependence
Dissection of the Phenotypic and Genotypic Associations With Nicotinic Dependence
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DOI：
10.1093/ntr/ntr231
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发表时间：
2012-04-01
影响因子：
4.7
通讯作者：
Bierut, Laura J.
中科院分区：
文献类型：
--
作者：
Chen, Li-Shiun;Baker, Timothy B.;Bierut, Laura J.
强有力的证据表明，尼古丁依赖与大规模全基因组关联研究中的4种遗传变异rs 16969968、rs6474412、rs3733829和rs 1329650相关。我们研究了这些识别出的遗传变异与尼古丁依赖的关系，这些依赖是通过不同的分类和维度测量来定义的。在2,047名欧洲血统的受试者（1,062例病例和985例对照）中分析了四种遗传变异。采用多种吸烟指标评估尼古丁依赖，包括Fagerstrom尼古丁依赖试验、精神疾病诊断与统计手册-IV（DSM-IV）尼古丁依赖、尼古丁依赖综合征量表和威斯康星州吸烟依赖动机量表。还检查了每天吸烟量（CPD）和早上第一支烟的时间（TTF）的单项指标。在变量中，rs 16969968的关联效应量最大，渴望和大量吸烟的指标，特别是每天吸烟的卷烟，显示出最大的影响。发现rs6474412和rs3733729之间存在显著但较弱的关联，但rs 1329650没有。没有更全面的吸烟行为的措施产生更强的遗传关联与这些变异比CPD。CPD是一个重要的简单的措施，捕捉部分CHRNA 5和尼古丁依赖的遗传关联，即使当其他更全面的吸烟行为的措施进行检查。CHRNA 5基因与重度强迫性吸烟和烟瘾有关;这应该为提高DSM-V诊断有效性的使命提供信息。
Strong evidence demonstrates that nicotine dependence is associated with 4 genetic variants rs16969968, rs6474412, rs3733829, and rs1329650 in large-scale Genome-Wide Association Studies. We examined how these identified genetic variants relate to nicotine dependence defined by different categorical and dimensional measures.Four genetic variants were analyzed in 2,047 subjects of European descent (1,062 cases and 985 controls). Nicotine dependence was assessed with multiple smoking measures, including the Fagerstrom Test for Nicotine Dependence, the Diagnostic and Statistical Manual for Mental Disorders-IV (DSM-IV) nicotine dependence, the Nicotine Dependence Syndrome Scale, and the Wisconsin Inventory of Smoking Dependence Motives. Single-item measures of cigarettes per day (CPD) and time to first cigarette (TTF) in the morning were also examined.Among the variants, association effect sizes were largest for rs16969968, with measures of craving and heavy smoking, especially cigarettes smoked per day, showing the largest effects. Significant but weaker associations were found for rs6474412 and rs3733729 but not for rs1329650. None of the more comprehensive measures of smoking behaviors yielded stronger genetic associations with these variants than did CPD.CPD is an important simple measure that captures in part the genetic associations of CHRNA5 and nicotine dependence, even when other more comprehensive measures of smoking behaviors are examined. The CHRNA5 gene is associated with heavy compulsive smoking and craving; this should inform the mission to improve the diagnostic validity of DSM-V.