Multi-Omics Study Identifies Genes Associated with Alcohol Use Disorder

Researchers from the Icahn School of Medicine at Mount Sinai used a multi-omics approach to identify a list of causal candidate genes associated with alcohol consumption and alcohol use disorder (AUD). Their study, published today in Nature Communications, also shows a potential link between alcoholism, Alzheimer’s disease, and other neurodegenerative disorders.

While previous studies identified loci associated with alcohol consumption, this study aimed to identify the variants and genes themselves. “Identification of causal variants and genes underlying genome-wide association study (GWAS) loci is essential to understand the biology of alcohol use disorder and to improve its treatment,” said first author Manav Kapoor.  

To identify genes relevant to AUD and drinks per week (DPW), a measure used to evaluate alcohol consumption, the research team integrated multi-omics data, using Mendelian Randomization-based methods on the largest available transcriptomic and epigenomic data from brain tissues and myeloid cells. Using data derived from these tissues, the team fine mapped complex loci and identified likely variants and candidate genes, including SPI1 and MAPT genes, associated with alcoholism. SPI1 and MAPT have also been found to be associated with susceptibility for other psychiatric and neurodegenerative disorders including depression and Alzheimer’s disease.

“This work could lead to novel therapeutics for the treatment for alcohol use disorders,” said senior author Alison Goate. “A number of anti-tau therapeutics are being developed for treatment of tauopathies including Alzheimer's disease, these should also be tested in AUD models.”