Variants Located Upstream of CHRNB4 on Chromosome 15q25.1 Are Associated with Age at Onset of Daily Smoking and Habitual Smoking

Authors

Manav Kapoor, Washington University School of Medicine in St. Louis
Jen-Chyong Wang, Washington University School of Medicine in St. Louis
Sarah Bertelsen, Washington University School of Medicine in St. Louis
Kathy Bucholz, Washington University School of Medicine in St. Louis
John P. Budde, Washington University School of Medicine in St. Louis
Anthony Hinrichs, Washington University School of Medicine in St. Louis
Arpana Agrawal, Washington University School of Medicine in St. Louis
Andrew Brooks, Rutgers University
David Chorlian, Downstate Medical Center
Danielle Dick, Virginia Commonwealth UniversityFollow
Victor Hesselbrock, University of Connecticut
Tatiana Foroud, Indiana University
John Kramer, University of Iowa
Sammuel Kuperman, University of Iowa
Niklas Manz, SUNY Downstate Medical Center
John Numberger Jr, University of Iowa
Bernice Porjesz, SUNY Downstate Medical Center
John Rice, Washington University
Jay Tischfield, Rutgers University - New Jersey
Xiaoling Xuei, Indiana University
Marc Schuckit, University of California San Diego
Haward J. Edenberg, Indiana University
Laura J. Bierut, Washington University
Alison M. Goate, Washington University

Document Type

Article

Original Publication Date

2012

Journal/Book/Conference Title

PLOS ONE

Volume

7

DOI of Original Publication

10.1371/journal.pone.0033513

Comments

Originally Published at : http://dx.doi.org/10.1371/journal.pone.0033513

Date of Submission

November 2014

Abstract

Several genome-wide association and candidate gene studies have linked chromosome 15q24–q25.1 (a region including the CHRNA5-CHRNA3-CHRNB4 gene cluster) with alcohol dependence, nicotine dependence and smoking-related illnesses such as lung cancer and chronic obstructive pulmonary disease. To further examine the impact of these genes on the development of substance use disorders, we tested whether variants within and flanking theCHRNA5-CHRNA3-CHRNB4 gene cluster affect the transition to daily smoking (individuals who smoked cigarettes 4 or more days per week) in a cross sectional sample of adolescents and young adults from the COGA (Collaborative Study of the Genetics of Alcoholism) families. Subjects were recruited from families affected with alcoholism (either as a first or second degree relative) and the comparison families. Participants completed the SSAGA interview, a comprehensive assessment of alcohol and other substance use and related behaviors. Using the Quantitative trait disequilibrium test (QTDT) significant association was detected between age at onset of daily smoking and variants located upstream of CHRNB4. Multivariate analysis using a Cox proportional hazards model further revealed that these variants significantly predict the age at onset of habitual smoking among daily smokers. These variants were not in high linkage disequilibrium (0.28CHRNB4 with onset of chronic smoking behaviors in adolescents and young adults and may improve genetic information that will lead to better prevention and intervention for substance use disorders among adolescents and young adults.

Rights

Copyright: © 2012 Kapoor et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Is Part Of

VCU Psychiatry Publications