Study on the Genetics of Alcoholism (COGA): Smoke screen and exome sequencing

This 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 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.

• Study Weblinks:
  • COGA
• Study Design:
  • Family/Twin/Trios
• Study Type:
  • Family
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 7148
• Subject Sample Telemetry Report (SSTR)

• BioProject
• BioSample
• MeSH

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 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: Indiana, New York, St. Louis, Connecticut, Iowa, San Diego.

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.

Prior COGA samples at dbGaP include case/control, EU families, and AA families. This subset of COGA is part of the NIDA Smokescreen Initiative. The Smokescreen® Genotyping Array by BioRealm® was created with support of a NIDA SBIR contract. The chip consists of an Affymetrix backbone with over 800,000 SNPs. The chip covers 98% of common genetic variation in 1000 nominated addiction genes. The chip contains 296,000 markers from African, East Asian, and European populations giving 66% coverage for people of African Ancestry, 82% for people of East Asian Ancestry, and 91% for people of European ancestry. In addition, 20,000 markers from expert nominations for genes posited to be associated with substance abuse and co-morbid disorders are also included on the chip. In addition, included in the array are more than 11,000 markers in the nicotine acetylcholine receptor gene clusters and nicotine metabolizing genes. There are greater than 16,000 markers for related co-morbidities and diseases. The current COGA Smokescreen sample was genotyped in two batches, and combined in a single set of files.

The other samples in Smokescreen will be released separately by contributing investigators, with ultimately a total of approximately 50,000 targeted.

In addition, exome sequencing data on a subset of individuals with GWAS were added in v2.

• Primary Phenotype: Alcoholism

• Principal Investigator
  • Bernice Porjesz, Ph.D. SUNY Downstate Medical Center, Brooklyn, NY, USA.
• Funding Source
  • U10 AA008401. National Institutes of Health, Bethesda, MD, USA.