Journal article
A Risk Allele for Nicotine Dependence in CHRNA5 Is a Protective Allele for Cocaine Dependence
Biological psychiatry (1969), Vol.64(11), pp.922-929
2008
DOI: 10.1016/j.biopsych.2008.04.018
PMCID: PMC2582594
PMID: 18519132
Abstract
A nonsynonymous coding polymorphism, rs16969968, of the
CHRNA5 gene that encodes the alpha-5 subunit of the nicotinic acetylcholine receptor (nAChR) has been found to be associated with nicotine dependence. The goal of this study was to examine the association of this variant with cocaine dependence.
Genetic association analysis was performed in two independent samples of unrelated case and control subjects: 1) 504 European Americans participating in the Family Study on Cocaine Dependence (FSCD) and 2) 814 European Americans participating in the Collaborative Study on the Genetics of Alcoholism (COGA).
In the FSCD, there was a significant association between the
CHRNA5 variant and cocaine dependence (odds ratio = .67 per allele,
p = .0045, assuming an additive genetic model), but in the reverse direction compared with that previously observed for nicotine dependence. In multivariate analyses that controlled for the effects of nicotine dependence, both the protective effect for cocaine dependence and the previously documented risk effect for nicotine dependence were statistically significant. The protective effect for cocaine dependence was replicated in the COGA sample. In COGA, effect sizes for habitual smoking, a proxy phenotype for nicotine dependence, were consistent with those observed in FSCD.
The minor (A) allele of rs16969968, relative to the major G allele, appears to be both a risk factor for nicotine dependence and a protective factor for cocaine dependence. The biological plausibility of such a bidirectional association stems from the involvement of nAChRs with both excitatory and inhibitory modulation of dopamine-mediated reward pathways.
Details
- Title: Subtitle
- A Risk Allele for Nicotine Dependence in CHRNA5 Is a Protective Allele for Cocaine Dependence
- Creators
- Richard A Grucza - Department of Psychiatry, Washington University, Saint Louis, MissouriJen C Wang - Department of Psychiatry, Washington University, Saint Louis, MissouriJerry A Stitzel - Department of Integrative Physiology, Institute for Behavioral Genetics, University of Colorado, Boulder, ColoradoAnthony L Hinrichs - Department of Psychiatry, Washington University, Saint Louis, MissouriScott F Saccone - Department of Psychiatry, Washington University, Saint Louis, MissouriNancy L Saccone - Department of Genetics, Washington University, Saint Louis, MissouriKathleen K Bucholz - Department of Psychiatry, Washington University, Saint Louis, MissouriC. Robert Cloninger - Department of Psychiatry, Washington University, Saint Louis, MissouriRosalind J Neuman - Department of Psychiatry, Washington University, Saint Louis, MissouriJohn P Budde - Department of Psychiatry, Washington University, Saint Louis, MissouriLouis Fox - Department of Psychiatry, Washington University, Saint Louis, MissouriSarah Bertelsen - Department of Psychiatry, Washington University, Saint Louis, MissouriJohn Kramer - Department of Psychiatry, University of Iowa College of Medicine, Iowa City, IowaVictor Hesselbrock - Department of Psychiatry, University of Connecticut Health Center, Farmington, ConnecticutJay Tischfield - Department of Genetics, Rutgers, New Brunswick, New JerseyJohn I Nurnberger - Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IndianaLaura Almasy - Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TexasBernice Porjesz - Department of Psychiatry, SUNY Health Science Center at Brooklyn, Brooklyn, New YorkSamuel Kuperman - Department of Psychiatry, University of Iowa College of Medicine, Iowa City, IowaMarc A Schuckit - Department of Psychiatry, University of California at San Diego, La Jolla, CaliforniaHoward J Edenberg - Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IndianaJohn P Rice - Department of Psychiatry, Washington University, Saint Louis, MissouriAlison M Goate - Department of Psychiatry, Washington University, Saint Louis, MissouriLaura J Bierut - Department of Psychiatry, Washington University, Saint Louis, Missouri
- Resource Type
- Journal article
- Publication Details
- Biological psychiatry (1969), Vol.64(11), pp.922-929
- DOI
- 10.1016/j.biopsych.2008.04.018
- PMID
- 18519132
- PMCID
- PMC2582594
- NLM abbreviation
- Biol Psychiatry
- ISSN
- 0006-3223
- eISSN
- 1873-2402
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2008
- Academic Unit
- Psychiatry; Stead Family Department of Pediatrics
- Record Identifier
- 9984003457302771
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