Can Alcohol Consumption and Alcohol Use Disorder be Caused by Genes?

Large list of causal candidate genes associated with alcohol consumption and alcohol use disorder (AUD) has been published the first study of its kind in the field of addiction genetics using a multi-omics approach at the Icahn School of Medicine, Mount Sinai, published in the journal Nature Communications.

A potential link between alcoholism, Alzheimer’s disease, and other neurodegenerative disorders has also been laid forward by the study. Alcohol use disorders are associated with heightened morbidity and mortality. It is one of the complex, moderately heritable, psychiatric disorders.

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‘Large list of causal candidate genes associated with alcohol consumption and alcohol use disorder (AUD) has been revealed in a study of its kind in the field of addiction genetics using a multi-omics approach. ’

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Although earlier studies have identified loci (genetic regions) associated with alcohol consumption, the present study helps in identifying the variants and genes themselves.

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“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,” says first and co-corresponding author, Manav Kapoor. Ph.D., an Assistant Professor of Neuroscience and Genetics and Genomics at Mount Sinai at the time of the study.

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The study team integrated multi-omics data, using Mendelian Randomization-based methods to identify genes relevant to AUD. It was done on the largest available transcriptomic and epigenomic data from brain tissues and myeloid cells.

The study successfully mapped complex loci with the identification of close variants and candidate genes, including SPI1 and MAPT genes, associated with alcoholism.

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These SPI1 (Spi-1 Proto-Oncogene) and MAPT have also been found to be associated with susceptibility for other psychiatric and neurodegenerative disorders including depression and Alzheimer’s disease.

SPI1 gene may be a major reason for the enrichment of immune pathways in drinking behaviors. And the MAPT gene encodes the tau protein, which is known for its role in central nervous system disorders such as Alzheimer’s disease, frontotemporal dementia, Parkinson’s disease, and other neurodegenerative disorders known as tauopathies.

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“This work could lead to novel therapeutics for the treatment for alcohol use disorders. 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,” says senior author, Alison Goate, D.Phil., Professor of Genetics and Genomic Sciences and Neuroscience at Mount Sinai.

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