CIDR: Collaborative Study on the Genetics of Alcoholism Case Control Study

This is a case-control study of alcoholism, in which the subjects have been drawn from the Collaborative Study on the Genetics of Alcoholism (COGA), a large, ongoing family-based study that includes subjects from seven sites around the US. COGA has gathered detailed, standardized data on study participants, including diagnostic and neurophysiological assessments. This sample has already proved successful in identifying several genes that influence the risk for alcoholism and neurophysiological endophenotypes, which have been independently replicated. COGA data were included as part of two Genetic Analysis Workshops, and the phenotypes are familiar to the genetics community.

Alcoholic probands were recruited from treatment facilities, assessed by personal interview, and after securing permission, other family members were also assessed. A set of comparison families was drawn from the same communities as the families recruited through an alcoholic proband. Assessment involved a detailed personal interview developed for this project, the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA), which gathers detailed information on alcoholism related symptoms along with other drugs and psychiatric symptoms. Many participants also came to the laboratories for electroencephalographic studies. Neurophysiological features that have been shown to be useful endophenotypes for which we have linkage and in some cases association results are included on a subset of the case-control sample: the beta power of the resting electroencephalogram (EEG), the P3(00) amplitude of the visual event-related potential (ERP), and the theta and delta event-related oscillations (EROs) underlying the P3 (See Porjesz et al., 2005; Porjesz and Rangaswamy, 2007 for reviews).

A brief description of COGA is in Edenberg, H. J. (2002) The Collaborative Study on the Genetics of Alcoholism: an update. Alcohol Res Health 26, 214-218., Bierut, LJ, NL Saccone, JP Rice, A Goate, T Foroud, HJ Edenberg, L Almasy, PM Conneally, R Crowe, V Hesselbrock, T-K Li, JI Nurnberger, Jr, B Porjesz, MA Schuckit, J Tischfield, H Begleiter, and T Reich (2002) Defining alcohol-related phenotypes in humans: The Collaborative Study on the Genetics of Alcoholism. Alcohol Res Health 26, 208-213. Edenberg HJ and Foroud T (2006) The genetics of alcoholism: identifying specific genes through family studies. Addiction Biology 11, 386-396.

This case-control sample of biologically unrelated individuals was drawn from COGA subjects. All cases meet DSM-IV criteria for alcohol dependence. Controls are individuals who have consumed alcohol, but did not meet any definition of alcohol dependence or alcohol abuse, nor did they meet any DSM-IIIR or DSM-IV definition of abuse or dependence for other drugs (except nicotine). All cases and controls have undergone identical clinical assessments. Many individuals in this case-control sample have not previously been genotyped.

The Collaborative Study on the Genetics of Alcoholism (COGA) has four Co-Principal Investigators: B. Porjesz, V. Hesselbrock, H. Edenberg, L. Bierut. COGA includes nine different centers where data collection, analysis, and storage take place. The nine sites and Principal Investigators and Co-Investigators are: University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenberg, J. Nurnberger Jr., T. Foroud); University of Iowa (S. Kuperman); SUNY Downstate (B. Porjesz); Washington University in St. Louis (L. Bierut, A. Goate, J. Rice); University of California at San Diego (M. Schuckit); Howard University (R. Taylor); Rutgers University (J. Tischfield); Southwest Foundation (L. Almasy). Q. Max Guo serves as the NIAAA Staff Collaborator. This national collaborative study is supported by the NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the National Institute on Alcohol Abuse and Alcoholism, the NIH GEI (U01HG004438),and the NIH contract "High throughput genotyping for studying the genetic contributions to human disease" (HHSN268200782096C).

COGA has over 250 publications listed at www.niaaagenetics.org

• Study Weblinks:
  • NIAAA COGA
• Study Design:
  • Case-Control
• Study Type:
  • Case-Control
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 1945
• Subject Sample Telemetry Report (SSTR)

• BioProject
• PubMed
• BioSample
• MeSH
• PMC

Unrelated individuals were chosen based on diagnoses from the adult SSAGA and SSAGA2 interviews. All subjects consented to sharing their samples. Both cases and controls were assessed by trained interviewers using the Semi-Structured Assessment for the Genetics of Alcoholism, a poly-diagnostic instrument.

Cases were alcohol dependent by DSM-IV criteria (at every interview if interviewed more than once). Probands were preferentially selected. Cases could not come from control pedigrees.

Controls were unaffected for a wide range of dependence phenotypes at every interview (if interviewed more than once). Controls could not have any alcoholism-related diagnosis (abuse or dependence or harmful use), nor could they have DSM-IIIR or DSM-IV diagnoses of cocaine abuse or dependence, marijuana abuse or dependence, opioid abuse or dependence, sedative abuse or dependence, or stimulant abuse or dependence. Similarly, controls could not have ICD10 diagnoses of cocaine dependence, marijuana dependence, opiate dependence, sedative dependence, or stimulant dependence. Controls could not share a known common ancestor with a proband. Controls above the age of 25 years were preferentially selected.

COGA was initiated in 1989, with Henri Begleiter as the Principal Investigator and Theodore Reich as the Co-Principal Investigator for 15 years. In 2004, while Henri Begleiter remained the PI, 4 Co-PIs were put into place: Howard Edenberg, Victor Hesselbrock, Bernice Porjesz and Laura Bierut. In 2006, the structure of the leadership changed again, with these 4 scientific Co-PIs leading the project, and Bernice Porjesz additionally serving as the Administrative PI. In addition to Henri Begleiter and Theodore Reich, several past key members of COGA were T.K. Li, Raymond Crowe, Wendy Reich and C. Michael Conneally, who have moved on to new positions or have retired.

In 1990, Phase I of COGA began, systematically ascertaining probands in treatment within six catchment areas, located across the United States (Indiana, New York, St. Louis, Connecticut, Iowa, San Diego). Probands met criteria of alcohol dependence based upon personal interview using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA), a polydiagnostic instrument developed by COGA, and had at least two first-degree relatives available for evaluation. Over the next 5 years, affected probands and family members participated in the study. During this time, Control families with the same family structure were also ascertained from the community, to be representative of the general population; controls did not have to be unaffected individuals. All families completed the same battery of tests. A subset of families underwent neurophysiological assessments.

In Phase II, between 1995 and 1999, some recruitment of new families continued, and the first follow-up protocol (5 year) was initiated. Affected families were extended. Adult clinical interviews conducted at this time used the SSAGA2 (a slight modification of the SSAGA to meet new diagnostic criteria).

Phase III began in 1999, and was primarily an extension of Phase II with an emphasis on recruiting high-risk families with young children. At this time Howard University became an additional recruitment site.

In 2004, COGA began Phase IV, the prospective study of adolescents and young adults from pedigrees ascertained in Phases I-III, which is ongoing. Participants are reassessed every two years.

For more details, see zork.wustl.edu/niaaa/coga_instruments/resources.

• Primary Phenotype: Alcoholism

• Co-Principal Investigators (*Administrative PI)
  • Bernice Porjesz*, PhD. SUNY Downstate Medical Center, Brooklyn NY, USA.
  • Howard J. Edenberg, PhD. Indiana University School of Medicine, Indianapolis, IN, USA.
  • Laura J. Bierut, MD. Washington University School of Medicine, St. Louis, MO, USA.
  • Victor Hesselbrock, PhD. University of Connecticut Health Center, Farmington, CT, USA.
• Steering Committee
  • Bernice Porjesz*, PhD. SUNY Downstate Medical Center, Brooklyn NY, USA.
  • Howard J. Edenberg, PhD. Indiana University School of Medicine, Indianapolis, IN, USA.
  • Laura J. Bierut, MD. Washington University School of Medicine, St. Louis, MO, USA.
  • Victor Hesselbrock, PhD. University of Connecticut Health Center, Farmington, CT, USA.
  • Laura Almasy, PhD. Southwest Foundation, San Antonio, TX, USA.
  • Tatiana Foroud, PhD. Indiana University School of Medicine, Indianapolis, IN, USA.
  • Alison Goate, DPhil. Washington University School of Medicine, St. Louis, MO, USA.
  • Samuel Kuperman, MD. University of Iowa Hospitals, Iowa City, IA, USA.
  • John I. Nurnberger, Jr., MD, PhD. Indiana University School of Medicine, Indianapolis, IN, USA.
  • John Rice, PhD. Washington University School of Medicine, St. Louis, MO, USA.
  • Marc A. Schuckit, MD. University of California, San Diego, CA, USA.
  • Robert Taylor MD. Howard University, Washington, DC, USA.
  • Jay A. Tischfield, PhD. Rutgers University, Piscataway, NJ, USA.
  • Q. Max Guo, PhD. National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
• Other Analysts/Investigators
  • Kathleen Bucholz, PhD. Washington University School of Medicine, St. Louis, MO, USA.
  • Andrew Chen, MD, PhD. SUNY Downstate Medical Center, Brooklyn NY, USA.
  • Danielle Dick, PhD. Virginia Commonwealth University, Richmond, VA, USA.
  • Anthony Hinrichs, PhD. Washington University School of Medicine, St. Louis, MO, USA.
  • John Kramer, PhD. University of Iowa, Iowa City, IA, USA.
  • Madhavi Rangaswamy, PhD. SUNY Downstate Medical Center, Brooklyn NY, 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.
  • Yongqiang Tang, PhD. SUNY Downstate Medical Center, Brooklyn NY, USA.
  • Jen Chyong Wang, PhD. Washington University School of Medicine, St. Louis, MO, USA.
  • Leah Flury Wetherill. Indiana University School of Medicine, Indianapolis, IN, USA.
  • Xiaoling Xuei, PhD. Indiana University School of Medicine, Indianapolis, IN, USA.
• Institutions
  • Indiana University School of Medicine, Indianapolis, IN, USA.
  • SUNY Downstate Medical Center, Brooklyn NY, USA.
  • Washington University School of Medicine, St. Louis, MO, USA.
  • University of Connecticut, Farmington, CT, USA.
  • University of Iowa, Iowa City, IA, USA.
  • University of California, San Diego, CA, USA.
  • Rutgers University, Piscataway, NJ, USA.
  • Southwest Foundation, San Antonio, TX, USA.
  • Howard University, Washington, DC, USA.
  • Virginia Commonwealth University, Richmond, VA, USA.
• Funding Source
  • U10 AA008401. National Institute on Alcohol Abuse and Alcoholism (NIAAA) and National Institute on Drug Abuse (NIDA), National Institutes of Health, Bethesda, MD, USA.
• Funding Source for Genotyping
  • U10 AA008401. National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health, Bethesda, MD, USA.
  • U01HG004438. NIH GEI.
  • HHSN268200782096C. NIH contract "High throughput genotyping for studying the genetic contributions to human disease".
• Genotyping Center
  • Johns Hopkins University Center for Inherited Disease Research (CIDR), Baltimore, MD, USA.