The Collaborative Study on the Genetics of Alcoholism (COGA)

COGA is a family 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 for 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.

As part of COGA, a set of informative families was selected to have Genome-Wide Association data obtained within families. Genotyping was performed using the Illumina Human OmniExpress array 12.VI to genotype 2,282 subjects selected from 118 densely affected families. Genotyping was performed at the Genome Technology Access Center at Washington University School of Medicine in St. Louis. In addition, we also included genotypes for subjects (n=275 subjects) from these 118 families who were genotyped in a previous case-control GWAS using the Illumina 1M array. For quality control purposes, 51 of the 275 subjects were genotyped again on the Illumina Human OmniExpress array at the Washington University School of Medicine core facility.

• Study Weblinks:
  • COGA
• Study Design:
  • Family/Twin/Trios
• Study Type:
  • Family
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 3557
• Subject Sample Telemetry Report (SSTR)

• BioProject
• PubMed
• BioSample
• MeSH
• PMC

COGA recruited patients who were currently in a psychiatric inpatient or outpatient program for alcohol and/or chemical dependency. Detoxification must be complete before approaching the individual.

A potential proband: must not have used intravenous drugs more than 30 times in a lifetime and not within six months of screening, must not have any life-threatening illness other than alcohol-related terminal illnesses such as cirrhosis or Korsakoff's, must not be infected with the HIV virus, and his/her first-degree relatives must speak English, and live within one of the following six COGA catchment areas.

Each COGA site recruited Control families consisting of two living parents and three or more full siblings, aged 14 or older. The Control Probands and families were ascertained via random consecutive sampling from either HMOs or dental clinics. They were to be representative of the general population and do not have to be unaffected individuals. Therefore, a Control family would not be eliminated if alcoholism is present among any of its members.

We extend families through all affecteds, alive and dead, which means the standard protocol was administered to all first-degree relatives of all affecteds. If any of these relatives were affected, we extend to his/her first-degree relatives, and continue if any of them are affected. In addition, extension by leapfrogging over a living or dead unaffected into a branch containing at least two first-degree relatives of the "leapfrogee" who have 3 implications by history.

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.

• Primary Phenotype: Alcoholism

• Co-Principal Investigators
  • Bernice Porjesz*, PhD (*Administrative PI). SUNY Health Sciences 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 School of Medicine, 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 School of Medicine, Farmington, CT, USA.
  • Arpana Agrawal, PhD. Washington University School of Medicine, St. Louis, MO, USA.
  • Laura Almasy, PhD. University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
  • Andrew Brooks, PhD. Rutgers University, Piscataway, NJ, USA.
  • Kathleen Bucholz, PhD. Washington University School of Medicine, St. Louis, MO, USA.
  • Danielle Dick, PhD. Virginia Commonwealth University, Richmond, VA, USA.
  • Tatiana Foroud, PhD. Indiana University School of Medicine, Indianapolis, IN, USA.
  • Alison Goate, DPhil. Icahn School of Medicine at Mt. Sinai, New York, NY, USA.
  • John Kramer, PhD. University of Iowa, Iowa City, IA, 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.
  • Abbas Parsian, PhD. National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
  • Matt Reilly, PhD. National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
• Other Analysts/Investigators
  • Fazil Aliev, PhD. Virginia Commonwealth University, Richmond, VA, USA.
  • Sarah Bertelsen. Icahn School of Medicine at Mt. Sinai, New York, NY, USA.
  • John Budde. Washington University School of Medicine, St. Louis, MO, USA.
  • Grace Chan. University of Connecticut School of Medicine, Farmington, CT USA.
  • David B. Chorlian. SUNY Downstate Medical Center, Brooklyn NY, USA.
  • Manav Kapoor, PhD. Icahn School of Medicine at Mt. Sinai, New York, NY, USA.
  • Jeanette N. McClintick, PhD. Indiana University School of Medicine, Indianapolis, IN, USA.
  • Vivia McCutcheon, PhD. Washington University School of Medicine, St. Louis, MO, USA.
  • Niklas Manz, PhD. SUNY Downstate Medical Center, Brooklyn NY, USA.
  • Scott Saccone, PhD. Washington University School of Medicine, St. Louis, MO, USA.
  • Jessica Salvatore, PhD. Virginia Commonwealth University, Richmond, VA, USA.
  • Jen-Chyong Wang, PhD. Icahn School of Medicine at Mt. Sinai, New York, NY, USA.
  • Leah Wetherill. Indiana University School of Medicine, Indianapolis, IN, USA.
  • Xiaoling Xuei, PhD. Indiana University School of Medicine, Indianapolis, IN, USA.
• Funding Source
  • U10 AA008401. National Institutes of Health, Bethesda, MD, USA.