The purpose of the Nicotine Dependence Consortium is to identify genetic contributions to the development of nicotine dependence. This group brings together investigators from multidisciplinary fields with experience in state of the art genetic studies and nicotine dependence.
Overall Study Design
Genome Wide Association of Nicotine Dependence – NICSNP Project
This project was formed under the auspices of the NIDA Genetics Consortium. In 2004, NIDA announced a call for proposals for a genome wide association study. The Nicotine Dependence Consortium headed by Laura Bierut with colleagues Naomi Breslau, Pamela Madden, Ovide Pomerleau, Gary Swan, and John Rice was selected as the sample for genotyping, and Perlegen Sciences, Inc was chosen to perform the genotyping for this project. As part of this collaborative project, a suite of committees was formed to oversee and organize the project. In addition, this project has a commitment to data sharing to insure the greatest scientific use of these data.
Subjects: Samples of European Ancestry were selected from the studies headed by Drs. Bierut and Madden. Primary ascertainment was based on nicotine dependence.
Cases: Cases are defined by a commonly used definition of nicotine dependence, a Fagerstrom Test for Nicotine Dependence (FTND)score of 4 or more (maximum score of 10) (Heatherton et al., 1991).
Controls: Controls are defined as individuals who have been exposed to regular smoking (defined by smoking at least 100 cigarettes lifetime), yet have never become dependent (lifetime FTND=0).
Sample Description: The final sample consists of 1929 individuals who were successfully genotyped, 1050 cases probands and 879 control subjects. Average age 37 years.
Cases: 587 women and 463 men
Controls: 612 women and 267 men
Candidate Gene Genotyping: An expert committee selected candidate genes and approximately 4000 SNPs were allocated for this genotyping. The candidate genes were subdivided into an “A” list and all others. The “A” list has a higher prior probability of an association with smoking. Genes on the “A” list include the nicotinic receptors, nicotine metabolizing genes, and other candidate genes from the literature. 3713 SNPs were successfully genotyped in the candidate genes.
Genome Wide Association: Genotyping was performed in a two-stage design. Pooled case and control samples (approximate 1000 subjects) were genotyped with 2.2 million SNPs. The most significant SNPs (approximately 40,000) were selected for individual genotyping in the entire sample. 31960 SNPs were successfully genotyped.
Data Sharing
This project is committed to sharing data with the Scientific Community so that the most scientific use can be made with these data. Decisions on access to data, coordination of research efforts, and publication of scientific papers will be made by the Steering Committee during the proprietary period. The proprietary period is defined as 12 months after receipt of the final cleaned data set or at the time of publication (which ever is shorter).
There are three data sets for release:
Genome Wide Association genotyping results
Candidate Gene genotyping results
Phenotypic data (FTND, age, gender, site)
Subject Description
Subjects: Samples of European Ancestry were selected from the studies headed by Drs. Bierut and Madden. Primary ascertainment was based on nicotine dependence.
Cases: Cases are defined by a commonly used definition of nicotine dependence, a Fagerstrom Test for Nicotine Dependence (FTND) score of 4 or more (maximum score of 10) (Heatherton et al., 1991).
Controls: Controls are defined as as individuals who have been exposed to regular smoking (defined by smoking at least 100 cigarettes lifetime), yet have never become dependent (lifetime FTND=0).
Sample Description: The final sample consists of 1929 individuals who were successfully genotyped, 1050 cases probands and 879 control subjects. Average age 37 years.
Genotyping initially was performed in pools and follow up genotyping was performed in the entire sample.
Cases: 587 women and 463 men
Controls: 612 women and 267 men