CIDR, NCI, NIDA Sequencing of Targeted Genomic Regions Associated with Smoking

This study includes samples from two projects: Collaborative Genetic Study of Nicotine Dependence (COGEND; PI: Laura Bierut) and Genetic Study of Nicotine Dependence in African Americans (AAND; PI: Laura Bierut and Eric Johnson).

The majority of the COGEND subjects included in the current study overlap with the two datasets already available on dbGaP. GWAS data are available for COGEND subjects through the Study of Addiction: Genetics and Environment (SAGE), dbGaP study accession phs000092. It should be noted that the case definition in the SAGE study is DSM-IV alcohol dependence. GWAS data are available for additional COGEND subjects through The Genetic Architecture of Smoking and Smoking Cessation, dbGaP study accession phs000404.

The overall goal of this project is to apply deep sequencing to key genomic regions associated with nicotine dependence in order to accelerate the discovery of variation in molecular pathways that govern the development of nicotine dependence. The sample includes unrelated cases and controls of European American and African American descent. Cases are defined by a commonly used definition of nicotine dependence, a current score of 4 or more (maximum score of 10) on the Fagerstrom Test for Nicotine Dependence (FTND). Control status is defined as an individual who smoked at least 100 cigarettes during their lifetime, yet never became dependent (lifetime FTND<2). By selecting controls who smoked cigarettes, we focus on those genetic effects that are specific to the development of nicotine dependence.

COGEND: COGEND was initiated in 2001 as a three-part program project grant funded through the National Cancer Institute (NCI; PI: Laura Bierut). The three projects included a study of the familial transmission of nicotine dependence, a genetic study of nicotine dependence, and a study of the relationship of nicotine dependence with nicotine metabolism. The primary goal was to detect, localize, and characterize genes that predispose or protect an individual with respect to heavy tobacco consumption, nicotine dependence, and related phenotypes and to integrate these findings with the family transmission and nicotine metabolism findings. The primary design was a community based case-control study. Nicotine dependent cases and non-dependent, smoking controls were identified and recruited from Detroit and St. Louis. More than 54,000 subjects aged 25-44 years were screened by telephone; more than 3,100 subjects were personally interviewed; and more than 2,900 subjects donated blood samples for genetic studies.

AAND: AAND was initiated in 2009 to identify and characterize genetic determinants of nicotine dependence in a large African American population. Community-based recruitment of approximately 100,000 people was conducted to ascertain 1,000 African American nicotine dependent cases and 1,000 African American non-dependent, smoking controls. All subjects were between the ages of 25-44. Subjects were screened by telephone; if they qualified as a case or control, they completed the same interview that was used in COGEND and donated a blood sample.

Both studies (COGEND and AAND) included measures of basic socio-demographic variables, including age, sex, race/ethnicity, family income, and educational attainment using the Semi-Structured Assessment for the Genetics of Nicotine Dependence. Information on nicotine dependence, as assessed by the Fagerstrom Test for Nicotine Dependence (FTND) is available for all subjects. In addition, participants also completed the Nicotine Dependence Syndrome Scale (NDSS; Shiffman et al., 2004) and the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68; Piper et al, 2004). All subjects were assessed in person by trained research assistants.

• Study Weblinks:
  • COGEND
• Study Design:
  • Case-Control
• Study Type:
  • Case-Control
• Total number of consented subjects: 2969
• Subject Sample Telemetry Report (SSTR)

• BioProject
• PubMed
• Sequence Read Archive
• BioSample
• MeSH
• PMC

Existing data and samples were selected from the Collaborative Genetic Study of Nicotine Dependence and the Genetic Study of Nicotine Dependence in African Americans. Cases are defined by a commonly used definition of nicotine dependence, a current FTND score of 4 or greater (maximum score of 10). Control status is defined as an individual who has smoked at least 100 cigarettes, but has never been dependent (lifetime FTND<2).

Subjects were excluded for any condition that would prevent effective participation in the protocol (e.g., language difficulties, CNS damage, or extremely poor health).

Permission to share data and samples was obtained from all subjects in the informed consent form. Informed consent was obtained from all subjects by trained research assistants. Prior to signing the consent form, a research assistant reviewed the form with the subject and answered any questions.

COGEND was initiated in 2001 as a three-part program project grant funded through the National Cancer Institute (PI: Laura Bierut). The three projects included a study of the familial transmission of nicotine dependence, a genetic study of nicotine dependence, and a study of the relationship of nicotine dependence with nicotine metabolism. The primary goal was to detect, localize, and characterize genes that predispose or protect an individual with respect to heavy tobacco consumption, nicotine dependence, and related phenotypes and to integrate these findings with the family transmission and nicotine metabolism findings. The primary design was a community based case-control study.

Nicotine dependent and control probands were recruited from the community using the Missouri Family Registry in St. Louis, MO and Health Maintenance Organizations in Detroit, MI. Nicotine dependent cases were identified during telephone screening as current smokers with a Fagerstrom Test for Nicotine Dependence (FTND) score of 4 or greater (maximum score of 10). Control subjects were identified during telephone screening as smokers (individuals who smoked at least 100 cigarettes lifetime), who never had any symptoms of dependence (lifetime FTND<2). All subjects had to be between the ages of 25 to 44 years and speak English. Subjects could not have a condition that prevented them from providing informed consent or effectively participating in the protocol (e.g., language difficulty, CNS damage, or extremely poor health).

All subjects were assessed using the Semi-Structured Assessment of Nicotine Dependence (SSAND), which was developed specifically for COGEND and is modeled after the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) and Composite International Diagnostic Interview (CIDI).

For more details, see http://zork5.wustl.edu/cogend/

AAND was initiated in 2009 to identify and characterize genetic determinants of nicotine dependence in a large African American population. Community-based recruitment of approximately 100,000 people was conducted in Chicago, IL, with the goal of ascertaining African American nicotine dependent cases and African American non-dependent, smoking controls. All subjects were between the ages of 25-44. Subjects were screened by telephone; if they qualified as a case or control, they completed the SSAND and donated a blood sample.

• Primary Phenotype: Tobacco Use Disorder
• Smoking Cessation
• Smoking

• Principal Investigator
  • Laura J. Bierut, MD. Washington University School of Medicine, St. Louis, MO, USA.
• Co-Investigator
  • Naomi Breslau, PhD. Michigan State University, East Lansing, MI, USA.
  • Li-Shiun Chen, MD. Washington University School of Medicine, St. Louis, MO, USA.
  • Robert Culverhouse, PhD. Washington University School of Medicine, St. Louis, MO, USA.
  • Alison Goate, DPhil. Icahn School of Medicine at Mt. Sinai, New York, NY, USA.
  • Richard Grucza, PhD. Washington University School of Medicine, St. Louis, MO, USA.
  • Dorothy Hatsukami, PhD. University of Minnesota, Minneapolis, MN, USA.
  • Eric O. Johnson, PhD. Research Triangle Institute International, Research Triangle Park, NC, USA.
  • John Rice, PhD. Washington University School of Medicine, St. Louis, MO, USA.
  • Nancy Saccone, PhD. Washington University School of Medicine, St. Louis, MO, USA.
  • Scott Saccone, PhD. Washington University School of Medicine, St. Louis, MO, USA.
  • Jen-Chyong Wang, PhD. Icahn School of Medicine at Mt. Sinai, New York, NY, USA.
• Funding Source
  • P01 CA089392. National Institutes of Health, Bethesda, MD, USA.
  • R01 DA025888. National Institutes of Health, Bethesda, MD, USA.
• Genotyping Center Funding Source
  • HHSN268201100011I. National Institutes of Health, Bethesda, MD, USA.
• Genotyping Center
  • Center for Inherited Disease Research (CIDR). Johns Hopkins University, Baltimore, MD, USA.
• Institute
  • National Cancer Institute, Bethesda, MD, USA.
  • National Institute on Drug Abuse, Bethesda, MD, USA.