Year: 2024
Type: article
Abstract: Background: At the invitation of the Journal, we are providing a summary of our published work that has followed the publication in 2009 of our manuscript entitled "Genetical Genomic Determinants of Alcohol Consumption in Rats and Humans". Our initial premise, which has been maintained throughout, is that knowledge regarding gene transcription would greatly enhance GWAS of alcohol-related phenotypes. We chose to concentrate our studies on the quantitative phenotype of alcohol consumption since high levels of alcohol consumption are a prerequisite for the development of alcohol use disorder (AUD). We also structured our studies to focus on "predisposition" to higher levels of alcohol consumption. We defined predisposition as a genetic structure and transcriptional pattern that is inherent in an organism and present prior to exposure to an environmental stimulus that engenders a physiological/behavioral response. In studies using humans, this interest in predisposition usually requires prolonged periods of cohort follow-up. On the other hand, studies with animals can use resources such as panels of recombinant inbred (RI) animals (in our case, the HXB/BXH rat panel) to capture the transcriptional landscape of animals not exposed to alcohol and compare this transcriptional landscape to levels of alcohol consumption collected from a different cohort of animals that are the same age, have an identical genetic composition, and are raised in an identical environment. The other benefit is that the stable genetic structure of inbred strains allows for a chronological expansion of information on these animals. This characteristic of the HXB/BXH RI rats allowed us to add important information as technology and analytical methods developed over time. Methods findings and conclusions: that repeatedly appeared within a gene coexpression module associated with alcohol consumption levels. Interestingly, data from post-mortem tissue from brain of humans suffering from AUD also indicates a hyperactive neuroimmune function. The data from studies with animals may indicate that neuroimmune hyperactivity may be a trait rather than a state marker for AUD.
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4404187947