Genome-Wide Association for Smoking Cessation Success: Participants in a Trial with Adjunctive Denicotinized Cigarettes

The ability to quit smoking successfully displays substantial heritability in classical and molecular genetic studies. Twin studies suggest that some of the genetics for the ability to quit overlap with genetic components of nicotine dependence, but many do not. Genome-wide association (GWA) studies have demonstrated haplotypes that distinguish successful quitters from individuals who were not able to quit smoking in: i) clinical trials that employed nicotine replacement; ii) clinical trials that employed bupropion; and iii) community quitter samples. We now report novel GWA results from participants in a clinical trial that document the efficacy of adjunctive use of denicotinized cigarettes. These results buttress data from our prior GWA studies of smoking cessation. They suggest that ability to change smoking behavior using denicotinized cigarettes shares substantial underlying genetics with the ability to change this behavior in community settings or in response to treatments with nicotine replacement or bupropion.

[1]  D. Hamer,et al.  Genome-Wide Association for Nicotine Dependence and Smoking Cessation Success in NIH Research Volunteers , 2009, Molecular medicine.

[2]  Chuan-Yun Li,et al.  Molecular Genetics of Addiction and Related Heritable Phenotypes , 2008, Annals of the New York Academy of Sciences.

[3]  A. Albino,et al.  A randomized trial of nicotine replacement therapy in combination with reduced-nicotine cigarettes for smoking cessation. , 2008, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[4]  Caryn Lerman,et al.  Molecular genetics of successful smoking cessation: convergent genome-wide association study results. , 2008, Archives of general psychiatry.

[5]  G. Mills,et al.  Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1 , 2008, Nature Genetics.

[6]  Daniel F. Gudbjartsson,et al.  A variant associated with nicotine dependence, lung cancer and peripheral arterial disease , 2008, Nature.

[7]  M. Iyo,et al.  Genome-wide association for methamphetamine dependence: convergent results from 2 samples. , 2008, Archives of general psychiatry.

[8]  Scott F. Saccone,et al.  Novel genes identified in a high-density genome wide association study for nicotine dependence. , 2007, Human molecular genetics.

[9]  G. Uhl,et al.  Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs , 2007, BMC Genetics.

[10]  Tomas Drgon,et al.  Addiction molecular genetics: 639,401 SNP whole genome association identifies many “cell adhesion” genes , 2006, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[11]  Tatiana Foroud,et al.  Pooled association genome scanning for alcohol dependence using 104,268 SNPs: Validation and use to identify alcoholism vulnerability loci in unrelated individuals from the collaborative study on the genetics of alcoholism , 2006, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[12]  J. Kaprio,et al.  Genetic Architecture of Smoking Behavior: A Study of Finnish Adult Twins , 2006, Twin Research and Human Genetics.

[13]  Tomas Drgon,et al.  Pooled association genome scanning: validation and use to identify addiction vulnerability loci in two samples. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[14]  N. Martin,et al.  Defining nicotine dependence for genetic research: evidence from Australian twins , 2004, Psychological Medicine.

[15]  D. Naiman,et al.  Polysubstance abuse-vulnerability genes: genome scans for association, using 1,004 subjects and 1,494 single-nucleotide polymorphisms. , 2001, American journal of human genetics.

[16]  K. Kendler,et al.  Multivariate assessment of factors influencing illicit substance use in twins from female-female pairs. , 2000, American journal of medical genetics.

[17]  M C Neale,et al.  Illicit psychoactive substance use, heavy use, abuse, and dependence in a US population-based sample of male twins. , 2000, Archives of general psychiatry.

[18]  M. Tsuang,et al.  Interrelationship of genetic and environmental influences on conduct disorder and alcohol and marijuana dependence symptoms. , 1999, American journal of medical genetics.

[19]  W D Plummer,et al.  Power and sample size calculations for studies involving linear regression. , 1998, Controlled clinical trials.

[20]  M. Tsuang,et al.  Co-occurrence of abuse of different drugs in men: the role of drug-specific and shared vulnerabilities. , 1998, Archives of general psychiatry.

[21]  A. Awad,et al.  Psychopharmacology: The Fourth Generation of Progress , 1998, CNS Spectrums.

[22]  George R. Uhl,et al.  D2 dopamine receptor Gene TaqI A1 and B1 restriction fragment length polymorphisms: Enhanced frequencies in psychostimulant-preferring polysubstance abusers , 1996, Biological Psychiatry.

[23]  N. Varney,et al.  Psychopharmacology: The Fourth Generation of Progress. , 1996 .

[24]  R Pickens,et al.  Genetic vulnerability to drug abuse. The D2 dopamine receptor Taq I B1 restriction fragment length polymorphism appears more frequently in polysubstance abusers. , 1992, Archives of general psychiatry.

[25]  W. Dupont,et al.  Power and sample size calculations. A review and computer program. , 1990, Controlled clinical trials.

[26]  D. Smith,et al.  Genetic vulnerability. , 1981, Science.