Collaborative Study on the Genetics of Alcoholism
The Collaborative Study on the Genetics of Alcoholism (COGA) is a tightly integrated, multifaceted and interdisciplinary project, with three overarching goals: to identify and characterize genes in which variations confer risk for (or protection from) the development of alcohol use disorders (AUDs) and related phenotypes; to understand the mechanisms by which these variants work at the molecular and cellular level; and to understand how genetic, environmental, and neurocognitive factors interact to influence the developmental trajectories of alcohol use and AUDs through an ongoing prospective study of at-risk individuals.
To accomplish these goals, COGA has assembled a team spanning a broad range of expertise, recruited a unique sample of large, ethnically diverse families densely affected by AUDs and a set of comparison families, and is carrying out a Prospective Study of adolescents and young adults from these families to elucidate how genetic risk unfolds across development against a background of documented environmental factors. We will continue our successful efforts to study a wide range of alcohol-related phenotypes, including neurophysiological endophenotypes, to maximize our power to detect novel variants/genes across the allelic spectrum. We will study the mechanism of action of newly identified genes to better understand how they affect risk and examine how the variants identified in one generation affect important precursor phenotypes and developmental trajectories during the critical adolescent/young adult phase of the next generation. At the same time, we will also explore how gender, ethnicity and environmental factors interact with these variants to moderate their effect on outcomes.The overarching specific aims of the molecular genetics component for the next five years of COGA are:
- To identify additional genes that contribute to the risk for AUD and related phenotypes
- To explore mechanisms of action of key genes
- To examine the effects of genes and environmental factors on clinical and neurophysiological phenotypes related to the vulnerability for risky drinking, AUDs and SUDs across adolescence and young adulthood.
We have recruited 2,255 families and 17,682 individuals, many from extended families denselyaffected with AUDs. This is the largest available family resource to develop novel endophenotypes and couple them with extensive genotyping and sequencing to identify novel allelic variants across the genome.
Kapoor M, Wang JC, Wetherill L, Le N, Bertelsen S, Hinrichs AL, Budde J, Agrawal A, Almasy L, Bucholz K, Dick DM, Harari O, Xiaoling X, Hesselbrock V, Kramer J, Nurnberger JI Jr, Rice J, Schuckit M, Tischfield J, Porjesz B, Edenberg HJ, Bierut L, Foroud T, Goate A.Genome-wide survival analysis of age at onset of alcohol dependence in extended high-risk COGA families. Drug Alcohol Depend. 2014 Sep 1;142:56-62. doi: 10.1016/j.drugalcdep.2014.05.023. Epub 2014 Jun 11. PMID: 24962325
Wang JC, Foroud T, Hinrichs AL, Le NX, Bertelsen S, Budde JP, Harari O, Koller DL, Wetherill L, Agrawal A, Almasy L, Brooks AI, Bucholz K, Dick D, Hesselbrock V, Johnson EO, Kang S, Kapoor M, Kramer J, Kuperman S, Madden PA, Manz N, Martin NG, McClintick JN, Montgomery GW, Nurnberger JI Jr, Rangaswamy M, Rice J, Schuckit M, Tischfield JA, Whitfield JB, Xuei X, Porjesz B, Heath AC, Edenberg HJ, Bierut LJ, Goate AM. v A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53. Mol Psychiatry. 2013 Nov;18(11):1218-24. doi: 10.1038/mp.2012.143. Epub 2012 Oct 23. PMID: 23089632