GENETICS OF SMOKING

NRL Research on the Genetics of Smoking

The University of Michigan Genetics of Smoking Integrated Database (GenSID) includes genotype and phenotype data drawn from several investigations on the genetics of smoking. When completed, it will include phenotypic and genotypic information on approximately 1800 related and unrelated individuals collected in connection with the following projects:

The Great Lakes Sibling Registry

The Great Lakes Sibling Registry (1999-2002) was funded by a grant from the National Cancer Institute to enroll families including one ever-smoking sibling, one never-smoking sibling, and two living parents. Extensive phenotypic assessments of susceptibility to nicotine dependence and other risk factors for smoking were collected on ~300 individuals.

Differentiation of Phenotypes for Smoking and Comparisons with Never-Smokers

This project was funded by an administrative supplement to a grant from the National Institute on Drug Abuse entitled Differentiation of Phenotypes for Smoking (1999-2005), making it possible for the project to participate in the NIDA Genetics Consortium. Blood samples were collected from 250-300 smokers (with high or low nicotine dependence and high or low depression), as well as from a comparable sample of 250-300 never-smokers (with high or low depression), matched for gender, race, age, and depressive status, for future genetic analysis.

Genetics of Smoking in Related and Unrelated Individuals

This project, funded by the National Institute on Drug Abuse in 2003, builds on both the above projects: a) Three hundred to four hundred trios (an ever-smoking proband residing in the Great Lakes region and two living parents) are being recruited to contribute DNA and phenotypic data to the NIDA Genetics Consortium. Trios who qualify from the Great Lakes Sibling Registry are also being invited to participate in the new project and to contribute the additional phenotypic data required for enrollment in the NIDA Genetics Consortium. b) The project also subsumes the case-control study already enrolled in the NIDA Genetics Consortium. The intent is to carry out genetic analyses, in both the trios and the cases and controls, to assess the relationship between presence or absence of alleles for several candidate genes (DRD2, DRD4, DAT1, nAChR alpha4, nAChR beta2, and CYP2A6) and variation in measures of nicotine dependence and cofactors.

The Perlegen Project

As a member of the NIDA Genetics Research Consortium, the Nicotine Research Laboratory is participating in a genome-wide association scan project for nicotine dependence in collaboration with the Perlegen Corporation. The project Genome wide association scan for nicotine dependence (Laura Bierut, Principal Investigator) utilizes immortalized cell lines being stored at the NIDA DNA registry at Rutgers University from subjects phenotyped at the University of Michigan, Washington University, and SRI International. The initial study will involve pooled genotyping of 1.6 million single nucleotide polymorphisms (SNPs), followed by individual genotyping of 40,000 SNPs and replication of findings in an independent sample.

NRL Publications on the Genetics of Smoking

Pomerleau OF (1995). Individual differences in sensitivity to nicotine: Implications for genetic research on nicotine dependence (invited article). Behavioral Genetics 25:161-177.

Pomerleau OF, Kardia SLR (1999). Health psychology and genetic research on smoking (invited commentary). Health Psychology 8:3-6.

Marks JL, Swan G, Pomerleau CS, Pomerleau OF (2003). Agreement between proband and parental self-report of smoking behavior. Nicotine and Tobacco Research 5:527-533.

Kardia SLR, Pomerleau CS, Rozek LS, Marks JL (2003). Association of parental smoking history with nicotine dependence, smoking rate, and psychological cofactors in adult smokers. Addictive Behaviors 28:1447-1452.

Etter J-F, Pelissolo A, Pomerleau CS, De Saint-Hilaire Z (2003). Associations between smoking and heritable temperament traits. Nicotine and Tobacco Research 5:401-409.

Pomerleau CS, Pomerleau OF, Snedecor SM, Mehringer AM (2004). Defining a never-smoker: Results from the Nonsmokers Survey. Addictive Behaviors 29:1149-1154.

Pomerleau CS, Pomerleau OF, Snedecor SM, Gaulrapp S, Kardia SLR (2004). Heterogeneity in phenotypes based on smoking status in the Great Lakes Smoker Sibling Registry. Addictive Behaviors 29:1851-1855.

Pomerleau CS, Snedecor S, Ninowski R, Gaulrapp S, Pomerleau OF, Kardia SLR (in press). Differences in accuracy of offspring assessment based on parental smoking status. Addictive Behaviors.

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