The collaborative study on the genetics of alcoholism: Genetics

Abstract

This review describes the genetic approaches and results from the family-based Collaborative Study on the Genetics of Alcoholism (COGA). COGA was designed during the linkage era to identify genes affecting the risk for alcohol use disorder (AUD) and related problems, and was among the first AUD-focused studies to subsequently adopt a genome-wide association (GWAS) approach. COGA's family-based structure, multimodal assessment with gold-standard clinical and neurophysiological data, and the availability of prospective longitudinal phenotyping continues to provide insights into the etiology of AUD and related disorders. These include investigations of genetic risk and trajectories of substance use and use disorders, phenome-wide association studies of loci of interest, and investigations of pleiotropy, social genomics, genetic nurture, and within-family comparisons. COGA is one of the few AUD genetics projects that includes a substantial number of participants of African ancestry. The sharing of data and biospecimens has been a cornerstone of the COGA project, and COGA is a key contributor to large-scale GWAS consortia. COGA's wealth of publicly available genetic and extensive phenotyping data continues to provide a unique and adaptable resource for our understanding of the genetic etiology of AUD and related traits.

Keywords: alcohol use disorder (AUD); alcoholism; family-based studies; genetic nurture; genome-wide association study (GWAS); longitudinal studies; polygenic scores (PGS); prospective studies; substance-related disorders; within-family comparisons.

FIGURE 1

Overview of genetically informed designs that have been used or are proposed for use in the COGA sample.

FIGURE 2

Graphical summary of three of the most important contributions to understanding the etiology of alcohol use disorders that have come, in part, from genetic analyses in COGA.