NCAM1-TTC12-ANKK1-DRD2 variants and smoking motives as intermediate phenotypes for nicotine dependence.
NCAM1-TTC12-ANKK1-DRD2 variants and smoking motives as intermediate phenotypes for nicotine dependence.
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DOI：
10.1007/s00213-014-3748-2
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发表时间：
2015-04
影响因子：
3.4
通讯作者：
MacKillop, J.
中科院分区：
文献类型：
--
作者：
Bidwell, L. C.;McGeary, J. E.;Gray, J. C.;Palmer, R. H. C.;Knopik, V. S.;MacKillop, J.
尼古丁依赖（ND）是一种具有复杂遗传影响的异质表型。使用中间 ND 表型可以阐明遗传影响并揭示特定的病因途径。先前的研究发现，威斯康星州吸烟动机清单 (WISDM) 的四个主要依赖动机 (PDM) 子量表（自动性、渴望性、失控性和耐受性）代表大量、普遍吸烟，这是尼古丁依赖的核心特征，使这些动机成为中间表型的有力候选者。本研究将 WISDM PDM 作为尼古丁依赖的新型中间表型进行了研究。该研究使用了 734 名每天至少吸 5 支烟 [M=16.2 (SD=9.5) 支/天] 的欧洲裔美国人的数据，完成了表型评估，并提供了 DNA 样本。基于染色体 11q23 上 NCAM1-TTC12-ANKK1-DRD2 区域遗传变异在吸烟行为中的作用的先前证据，使用单倍型和个体基因座方法检查了 12 个区域基因座与尼古丁依赖和 PDM 表型之间的关联。此外，中介分析测试了从遗传变异到吸烟动机再到尼古丁依赖的间接途径。 NCAM1-TTC12-ANKK1-DRD2 区域基因座和单倍型与自动化的动机显着相关，此外，自动化显着介导 NCAM1-TTC12-ANKK1-DRD2 簇变异和尼古丁依赖之间的关联。这些结果表明，与自动化相关的动机是理解遗传对尼古丁依赖的贡献的可行的中间表型。此外，NCAM1-TTC12-ANKK1-DRD2 变异可能会增加一个人通过高度自动的吸烟习惯而产生依赖性的可能性，而这种习惯在几乎没有意识的情况下就会引起。
Nicotine dependence (ND) is a heterogeneous phenotype with complex genetic influences. The use of intermediate ND phenotypes may clarify genetic influences and reveal specific etiological pathways. Prior work has found that the four Primary Dependence Motives (PDM) subscales (Automaticity, Craving, Loss of Control, and Tolerance) of the Wisconsin Inventory of Smoking Motives (WISDM) represent heavy, pervasive smoking, which is a core feature of nicotine dependence, making these motives strong candidates as intermediate phenotypes. This study examines the WISDM PDM as a novel intermediate phenotype of nicotine dependence. The study used data from 734 European Americans who smoked at least 5 cigs/day [M=16.2 (SD=9.5) cigs/day], completed a phenotypic assessment, and provided a sample of DNA. Based on prior evidence of the role of genetic variation in the NCAM1-TTC12-ANKK1-DRD2 region on chromosome 11q23 in smoking behavior, associations among 12 region loci with nicotine dependence and PDM phenotypes were examined using haplotype and individual loci approaches. In addition, mediational analysis tested the indirect pathway from genetic variation to smoking motives to nicotine dependence. NCAM1-TTC12-ANKK1-DRD2 region loci and haplotypes were significantly associated with the motive of Automaticity and, further, Automaticity significantly mediated associations among NCAM1-TTC12-ANKK1-DRD2 cluster variants and nicotine dependence. These results suggest that motives related to automaticity are a viable intermediate phenotype for understanding genetic contributions to nicotine dependence. Further, NCAM1-TTC12-ANKK1-DRD2 variants may increase the likelihood that a person will become dependent via a highly automatic smoking ritual that can be elicited with little awareness.
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影响因子：
2.1
作者：
Mota NR;Araujo-Jnr EV;Paixão-Côrtes VR;Bortolini MC;Bau CH
通讯作者：
Bau CH
影响因子：
11
作者：
Jönsson, EG;Nöthen, MM;Sedvall, GC
通讯作者：
Sedvall, GC
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
6
作者：
MacKillop, James;Few, Lauren R.;Chaloupka, Frank
通讯作者：
Chaloupka, Frank