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

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.