1. ¹Molecular Neurobiology Branch, NIH-IRP, NIDA, Baltimore, MD, USA
2. ²Department of Psychiatry and Behavioral Sciences, Center for Nicotine and Smoking Cessation Research, Duke University, Durham, NC, USA

Correspondence: Dr GR Uhl, Molecular Neurobiology, NIH-IRP, NIDA, Suite 3510, 333 Cassell Drive, Box 5180, Baltimore, MD 21224, USA. Tel.: +1 410 550 2843 146; Fax: +1 410 550 1535; E-mail: guhl@intra.nida.nih.gov

Received 18 April 2007; Revised 21 May 2008; Accepted 3 July 2008; Published online 9 September 2008.

Abstract

Twin studies document substantial heritability for successful abstinence from smoking. A genome-wide association study has identified markers whose allele frequencies differ with nominal P<0.005 in nicotine-dependent clinical trial participants who were successful vs unsuccessful in abstaining from smoking; many of these results are also supported by data from two additional samples. More study is required to precisely determine the variance in quitting success that can be accounted for by the single-nucleotide polymorphisms that are currently identified and to precisely classify individuals who may display varying degrees of genetic vs environmental effects into quitters or nonquitters. However, the data at hand do allow us to model the effects of genotypic stratification in smoking cessation trials. We identify relationships between the costs of identifying and genotyping prospective trial participants vs the costs of performing the clinical trials. We quantitate the increasing savings that result from genetically stratified designs as recruiting/genotyping costs go down and trial costs increase. This model helps to define the circumstances in which genetically stratified designs may enhance power and reduce costs for smoking cessation clinical trials.