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5. Collaborative Study on the Genetics of Alcoholism: Functional genomics.

Isabel Gameiro-Ros¹, Dina Popova², Iya Prytkova¹

¹Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Genes, Brain, and Behavior

|August 3, 2023

Summary

The Collaborative Study on the Genetics of Alcoholism (COGA) uses advanced methods to understand how genes influence Alcohol Use Disorder (AUD). Their research reveals mechanisms linking genetic risk variants to AUD, offering potential treatment targets.

Keywords:

alcohol use disorder (AUD)brain gene expression genomics induced pluripotent stem cells neuronal function

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Area of Science:

Genetics
Neuroscience
Pharmacology

Background:

Alcohol Use Disorder (AUD) is a complex genetic disorder influenced by genetic, neural, and environmental factors.
The Collaborative Study on the Genetics of Alcoholism (COGA) has identified potential AUD risk genes using genome-wide association studies.

Purpose of the Study:

To review COGA's advances in understanding functional changes caused by AUD risk genes.
To highlight the use of multimodal approaches with human cell lines and brain tissue to elucidate these mechanisms.

Main Methods:

Investigating gene regulation in lymphoblastoid cells and post-mortem brain tissues.
Employing high-throughput reporter assays to identify functional single nucleotide polymorphisms (SNPs).
Modeling specific SNPs using induced pluripotent stem cells (iPSCs) to assess effects on transcriptomics, neuronal function, and ethanol response.

Main Results:

Functional studies reveal how genetic variants impact gene expression and neuronal physiology in the context of AUD.
Integration of multimodal data from COGA participants and functional studies links genomic variations to AUD mechanisms.

Conclusions:

COGA's integrated approach successfully links genomic variants to AUD, providing insights into disease mechanisms.
These findings identify potential therapeutic targets for Alcohol Use Disorder treatments.