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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

Content Provider	Springer Nature Link
Author	Lubke, Gitta H. Stephens, Sarah H. Lessem, Jeffrey M. Hewitt, John K. Ehringer, Marissa A.
Copyright Year	2012
Abstract	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 (Greenbaum et al. 2009). 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.
Starting Page	636
Ending Page	646
Page Count	11
File Format	PDF
ISSN	00018244
Journal	Behavior Genetics
Volume Number	42
Issue Number	4
e-ISSN	15733297
Language	English
Publisher	Springer US
Publisher Date	2012-03-01
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Survival mixture analysis Nicotine initiation Substance use CHRNA5/B3/A4 cluster Public Health/Gesundheitswesen Health Psychology Clinical Psychology
Content Type	Text
Resource Type	Article
Subject	Genetics Ecology, Evolution, Behavior and Systematics Genetics (clinical)

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