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首页> 美国卫生研究院文献>other >The CHRNA5/A3/B4 Gene Cluster and Tobacco Alcohol Cannabis Inhalants and Other Substance Use Initiation: Replication and New Findings Using Mixture Analyses
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The CHRNA5/A3/B4 Gene Cluster and Tobacco Alcohol Cannabis Inhalants and Other Substance Use Initiation: Replication and New Findings Using Mixture Analyses

机译：ChrNA5 / A3 / B4基因簇和烟草酒精大麻吸入剂和其他物质使用引发：使用混合物分析来复制和新发现

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Multiple studies have provided evidence for genetic associations between single nucleotide polymorphisms (SNPs) located on the CHRNA5/A3/B4 gene cluster and various phenotypes related to Nicotine Dependence (). Only a few studies have investigated other substances of abuse. The current study has two aims, (1) to extend previous findings by focusing on associations between the CHRNA5/A3/B4 gene cluster and age of initiation of several different substances, and (2) to investigate heterogeneity in age of initiation across the different substances. All analyses were conducted with a subset of the Add Health study with available genetic data. The first aim was met by modeling onset of tobacco, alcohol, cannabis, inhalants, and other substance use using survival mixture analysis (SMA). Ten SNPs in CHRNA5/A3/B4 were used to predict phenotypic differences in the risk of onset, and differences between users and non-users. The survival models aim at investigating differences in the risk of initiation across the 5–18 age range for each phenotype separately. Significant or marginally significant genetic effects were found for all phenotypes. The genetic effects were mainly related to the risk of initiation and to a lesser extent to discriminating between users and non-users. To address the second goal, the survival analyses were complemented by a latent class analysis that modeled all phenotypes jointly. One of the ten SNPs was found to predict differences between the early and late onset classes. Taken together, our study provides evidence for a general role of the CHRNA5/A3/B4 gene cluster in substance use initiation that is not limited to nicotine and alcohol.
机译：多项研究提供了位于ChrNA5 / A3 / B4基因簇上的单核苷酸多态性（SNP）之间的遗传关联的证据，以及与尼古丁依赖性（）相关的各种表型。只有少数研究研究了其他滥用物质。目前的研究有两个目的，（1）通过专注于ChrNA5 / A3 / B4基因集群和起始年龄的结合来扩展先前的发现，（2）调查在不同的开始时代的异质性物质。所有分析都是通过添加健康研究的子集进行的，具有可用的遗传数据。使用存活混合物分析（SMA），通过建模烟草，酒精，大麻，吸入剂和其他物质使用的发作来满足第一个目的。 ChrNA5 / A3 / B4中的十个SNP用于预测发病风险的表型差异，以及用户和非用户之间的差异。生存模型旨在分别对每种表型患有5-18岁范围的启动风险的差异。对所有表型发现显着或略微显着的遗传效果。遗传效应主要与发起的风险有关，并在较小程度上歧视用户和非用户之间。为了解决第二个目标，通过潜在的阶级分析来补充生存分析，该阶级分析共同建立了所有表型。发现十个SNP中的一个可以预测早期和晚期开始阶段之间的差异。我们的研究占据了，我们的研究提供了ChrNA5 / A3 / B4基因簇中的一般作用的证据，其使用不限于尼古丁和醇。

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