Scientists from the Icahn School of Medicine at Mount Sinai published the first of its kind research in the field of addiction genetics employing a multi-omics method to offer a huge list of causal candidate genes linked with alcohol consumption and alcohol use disorder (AUD).
Alcohol Use. Image Credit: Firn/Shutterstock.com
The research also reveals a potential association between alcoholism, Alzheimer’s disease, and other neurodegenerative disorders. The results were published on August 20th, 2021, in the Nature Communications journal.
Alcohol use disorders are intricate, moderately heritable, psychiatric disorders linked with increased morbidity and mortality. Although earlier research works revealed the loci (genetic regions) linked with alcohol consumption, the current research intended to uncover 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.”
Manav Kapoor, PhD, Study First and Co-Corresponding Author and Assistant Professor, Neuroscience and Genetics and Genomics, Icahn School of Medicine at Mount Sinai
To discover genes relevant to AUD and drinks per week (DPW)—a measure employed to estimate alcohol consumption—the scientists merged multi-omics data, using Mendelian Randomization-based techniques on the biggest available transcriptomic and epigenomic data from myeloid cells and brain tissues.
The researchers used data acquired from these tissues to fine-map complex loci and found likely variants and candidate genes, including SPI1 and MAPT genes, linked with alcoholism. SPI1 and MAPT are also observed to be linked with susceptibility for other neurodegenerative and psychiatric disorders, including depression and Alzheimer’s disease.
SPI1 (Spi-1 Proto-Oncogene) encodes an ETS-domain transcription factor (PU.1) that can regulate gene expression during B-lymphoid and myeloid cell development and homeostasis. Given SPI1’s control over the expression of several downstream genes, this gene might be a significant reason for the improvement of immune pathways in drinking behaviors, as seen in a past transcriptomic analysis of human and animal brains.
The MAPT gene examined in the research encodes the tau protein, known for its role in central nervous system disorders like frontotemporal dementia, Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative disorders known as tauopathies.
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.”
Alison Goate DPhil, Study Senior Author and Professor, Genetics and Genomic Sciences and Neuroscience, Icahn School of Medicine at Mount Sinai
Dr Goate’s laboratory has also obtained funding to create inhibitors of SPI1 for Alzheimer’s Disease. Recent research indicates that these inhibitors may be beneficial for treating alcoholism.
Kapoor, M., et al. (2021) Multi-omics integration analysis identifies novel genes for alcoholism with potential overlap with neurodegenerative diseases. Nature Communications. doi.org/10.1038/s41467-021-25392-y.