The Collaborative Study on the Genetics of Alcoholism (COGA)

What is COGA?

COGA, the Collaborative Study On The Genetics of Alcoholism, is the most comprehensive research project ever to be conducted on the inherited aspects of alcoholism. This large-scale family study is designed to identify genes that affect the risk for alcoholism and alcohol-related characteristics and behaviors. Sponsored by the National Institue on Alcohol Abuse and Alcoholism, COGA is studying a large number of families at nine sites across the United States and has enlisted the support of some of our country's most experienced researchers. (see also COGA: An Update)

COGAs Goals

The multi-disciplinary, multi-center national COGA project intends to characterize the genetic factors involved in a predisposition to develop alcohol dependence and related phenotypes. The project established an archival database of comprehensive phenotypic assessments of families (clinical, neurophysiological), as well as lymphoblastoid cell lines for DNA. Genetic analyses (total genome scan: linkage analysis and candidate gene: linkage disequilibrium, Single Nucleotide Polymorphism (SNP) association) have yielded several important results, such as the involvement of a GABA_A receptor gene in neural excitability and predisposition to develop alcohol dependence.

COGAs research focusses on four primary areas, all of which are related to the overall goal of identifying genes that affect risk for or protection from alcoholism, and understanding the mechanisms by which they work.

1) The first goal is to further identify genes in which variants affect the risk for alcoholism and related disorders. Although COGA has been successful in identifying several genes, the nature of the disease is such that many more remain to be found. Our sample of severely affected subjects in genetically-loaded families has proven to be the premier engine of discovery. We have recently begun a Genome Wide Association Study of a case-control sample of adults, which should complement our family-based analyses.

2) Along with gene discovery, COGA will increase the efforts to identify functional variants in the associated genes and to understand their effects on molecular and cellular processes. These efforts are led by the two Molecular Genetics Laboratories and augmented by the capabilities of the NIAAA/COGA Sharing Repository.

3) The third major focus is the development and refinement of endophenotypes, an approach that has helped COGA in the identification of genes, and can help in understanding how they manifest in disease.

4) The fourth major focus is the study of adolescents and young adults, to examine genetic effects across development and to understand the factors that affect risk in this critical age range. A key component of this is the continuation of the prospective study, unique in its use of families in which specific alleles that affect risk have been identified (and more will be). COGA will explore how these variants manifest themselves as adolescents and young adults pass into and through the prime ages of risk for developing alcoholism and related diseases. This prospective study will gather key environmental data to allow examination of gene-environment interplay in the context of known genetic variants.

Co-Principal Investigators: B. Porjesz, SUNY Downstate Medical Center V. Hesselbrock, University of Connecticut H. Edenberg, Indiana University L. Bierut, Washington University
This collaborative study 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. Edenberg, J. Nurnberger, Jr., P.M. Conneally, T. Foroud
University of Iowa	S. Kuperman, R. Crowe
SUNY Downstate Medical Center	B. Porjesz
Washington University	L. Bierut, A. Goate, J. Rice
University of California (UCSD)	M. Schuckit
Howard University	R. Taylor
Rutgers University	J. Tischfield
Southwest Foundation	L. Almasy

Zhaoxia Ren, 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).

In memory of Henri Begleiter and Theodore Reich, Principal and Co-Principal Investigators of COGA since its inception; we are indebted to their leadership in the establishment and nurturing of COGA, and acknowledge with great admiration their seminal scientific contributions to the field.