Get access

Association of CHRNA4 polymorphisms with smoking behavior in two populations§

Authors

  • Shizhong Han,

    1. Department of Psychiatry, Division of Human Genetics, Yale University School of Medicine, New Haven, Connecticut
    2. VA CT Healthcare Center 116A2, 950 Campbell Avenue, West Haven, Connecticut
    Search for more papers by this author
  • Bao-Zhu Yang,

    1. Department of Psychiatry, Division of Human Genetics, Yale University School of Medicine, New Haven, Connecticut
    2. VA CT Healthcare Center 116A2, 950 Campbell Avenue, West Haven, Connecticut
    Search for more papers by this author
  • Henry R. Kranzler,

    1. Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    2. VISN 4 MIRECC, Philadelphia VAMC, Philadelphia, Pennsylvania
    Search for more papers by this author
  • David Oslin,

    1. Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    2. VISN 4 MIRECC, Philadelphia VAMC, Philadelphia, Pennsylvania
    Search for more papers by this author
  • Raymond Anton,

    1. Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina,
    Search for more papers by this author
  • Joel Gelernter

    Corresponding author
    1. Department of Psychiatry, Division of Human Genetics, Yale University School of Medicine, New Haven, Connecticut
    2. VA CT Healthcare Center 116A2, 950 Campbell Avenue, West Haven, Connecticut
    3. Department of Genetics, Yale University School of Medicine, New Haven, Connecticut
    4. Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut
    • Department of Psychiatry, Yale University School of Medicine, VA CT Healthcare Center, 950 Campbell Avenue, 116A2, West Haven, CT 06516.
    Search for more papers by this author

  • This article was published online on 28 March 2011. An error was subsequently identified with the affiliation of David Oslin being listed incorrect. This notice is included in the online and print versions to indicate that both have been corrected 21 April 2011.

  • Drs. Yang, Han, and Gelernter report no competing interests. Dr. Kranzler reports consulting arrangements with Gilead Sciences and Alkermes, Inc. and research support from Merck & Co. Dr. Kranzler also reports a current association with the following pharmaceutical companies: Eli Lilly, Janssen, Schering Plough, Lundbeck, Alkermes, GlaxoSmithKline, Abbott, and Johnson & Johnson, as these companies provide support to the Alcohol Clinical Trials Initiative (ACTIVE) and Dr. Kranzler receives support from ACTIVE.

  • §

    How to cite this article: Han S, Yang B-Z, Kranzler HR, Oslin D, Anton R, Gelernter J. 2011. Association of CHRNA4 Polymorphisms with Smoking Behavior in Two Populations. Am J Med Genet Part B 156:421–429.

Abstract

CHRNA4, the gene that encodes the nicotinic acetylcholine receptor α4 subunit, is a potential candidate gene for nicotine dependence (ND). However, studies of the association of CHNRA4 with smoking behavior have shown inconsistent results. Our meta-analysis of linkage studies of smoking behavior identified a genome-wide significant linkage of the phenotype maximum number of cigarettes smoked in a 24-hour period to a region (20q13.12-q13.32) harboring CHRNA4. This motivated us to examine the association of CHRNA4 with smoking behavior in two independent samples. In this study, we examined five single nucleotide polymorphisms (SNPs) within CHRNA4 and three smoking-related behaviors: one quantitative trait [cigarettes smoked per day (CPD)], and two binary traits [DSM-IV diagnosis of ND and dichotomized Fagerstrom test of ND (FTND)], in 1,249 unrelated European-Americans (EAs) and 1,790 unrelated African-Americans (AAs). Using the combined sample with sex, age, and race as covariates, the synonymous SNP rs1044394 was significantly associated with ND (P = 0.001) and FTND (P = 0.01). Rs2236196, which has a low correlation with rs1044394, was also significantly associated with CPD (P = 0.003). The pattern of association for these SNPs was similar in AAs and EAs. After correction for multiple testing, the association between rs1044394 and ND in the combined sample remained significant (P = 0.033). In summary, our study supports association between CHRNA4 common variation and ND in AA and EA samples. Additional studies will be necessary to evaluate the role of rare variants at CHRNA4 for ND. © 2011 Wiley-Liss, Inc.

Ancillary