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 project 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.In addition, exome sequencing data on a subset of individuals with GWAS were added in version 2 (v2). For v2, a subset had 30X Whole Genome Sequencing (WGS) as part of the NIDA Sequencing Initiative. The subset contained two distinct sets: Sibling pairs where one sibling had at least two dependence diagnoses in the set (alcohol, cannabis, cocaine, and opioid), and the other had none, and non-related Case-Control pairs matched for age and ethnicity where the cases had alcohol and at least 2 other dependence diagnoses and controls had none. After sequencing, some sibling pairs are re-classified as half siblings. Three VCF files (small variants, structural variants, and copy number variations) are provided. Additional substance use variables are made available in v2. We note that the full sample data are deposited in four dbGaP submissions and the sequenced samples are split across all four: CIDR: Collaborative Study on the Genetics of Alcoholism Case Control Study [phs000125]. GWAS data on cases (primarily probands) and controls drawn from the families. Families with highest density of alcohol dependence and/or extreme event-related oscillation data [phs000763]. GWAS data on 119 extended families of European descent are available here, along with extensive documentation. Study on the Genetics of Alcoholism (COGA): African American Family GWAS [phs000976]. GWAS data on all available COGA families of African descent are available. COGA: Smokescreen GWAS [phs001208]. GWAS data on all remaining COGA DNA samples, primarily of other racial background, were genotyped on the Smoke Screen array. A listing of all sequenced pairs is provided in the documentation to facilitate the merging of these samples. ]]>
Visual Oddball Experiment and Event-Related Oscillations (ERO)The goal of the present study was to perform a genome-wide association study (GWAS) in extended families from the Collaborative Study on the Genetics of Alcoholism to identify novel genes affecting risk for alcohol dependence (AD). To maximize the power of the extended family design, we used a quantitative endophenotype, measured in all individuals: number of alcohol-dependence symptoms endorsed (symptom count (SC)). Secondary analyses were performed to determine if the single nucleotide polymorphisms (SNPs) associated with SC were also associated with the dichotomous phenotype, DSM-IV AD. To reduce the heterogeneity in the sample, only families that were primarily of Caucasian descent were selected for genotyping, yielding a total of 2322 subjects from 118 extended families who were genotyped.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: Indiana, New York, St. Louis, Connecticut, Iowa, and 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 extended families through all affected, alive and dead, which means the standard protocol was administered to all first-degree relatives of all affected members. If any of these relatives were affected, we extended to his/her first-degree relatives, and continued if any of them was affected. In addition, extension by leapfrogging over a living or dead unaffected went to a branch containing at least two first-degree relatives of the "leapfrog" who had 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, and San Diego). Probands met criteria of alcohol dependence based upon personal interview using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA), a poly diagnostic 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.]]>