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Henri Begleiter Neurodynamics Laboratory

Novel Phenotypes for the Genetic Analysis of Alcoholism

This project develops novel neurophysiological phenotypes involving brain oscillations that are highly heritable and can be used in studying the genetics of alcoholism.

We are studying the functional neuroanatomical correlates in an associated fMRI study on individuals at risk. In the coming years we plan to use the neurophysiological phenotypes developed in this project for the genetic project described above.

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 Institute 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)

COGA's 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 GABAA receptor gene in neural excitability and predisposition to develop alcohol dependence.

COGA's 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.

The Collaborative Study on the Genetics of Alcoholism (COGA)

Principal Investigators:
B. Porjesz, SUNY Downstate Medical Center
V. Hesselbrock, University of Connecticut
H. Edenberg, Indiana University
L. Bierut, Washington University

COGA includes nine different centers:

University of Connecticut V. Hesselbrock
Indiana University H.J. Edenberg, J. Nurnberger, Jr., T. Foroud
University of Iowa S. Kuperman, J. Kramer
SUNY Downstate Medical Center B. Porjesz
Washington University in St. Louis L. Bierut, A. Goate, J. Rice, K. Buchholz
University of California at San Diego M. Schuckit
Rutgers University J. Tischfield
Texas Biomedical Research Institute L. Almasy
Virginia Commonwealth University D. Dick

Other COGA collaborators include:

University of Connecticut L. Bauer
Indiana University D. Koller, S. O'Connor, L. Wetherill, X. Xuei
University of Iowa G. Chan
SUNY Downstate Medical Center N. Manz, M. Rangaswamy
Washington University in St. Louis A. Hinrichs, J. Rohrbaugh, J.-C. Wang
Rutgers University A. Brooks
Virginia Commonwealth University F. Aliev

A. Parsian and M. Reilly are the NIAAA Staff Collaborators.

We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding PI and Co-PI of COGA, and also owe a debt of gratitude to other past organizers of COGA, including Ting-Kai Li, currently a consultant with COGA, P. Michael Conneally, Raymond Crowe, and Wendy Reich, for their critical contributions.
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).