Genetics of gene expression characterizes response to selective breeding for alcohol preference

Area of Science:

• Neurogenetics
• Behavioral Genetics
• Genomics

Background:

• Understanding the genetic underpinnings of alcohol preference is crucial for addressing alcohol use disorders.
• Selective breeding experiments in rodents have historically identified genetic factors influencing alcohol consumption.
• Gene expression differences are increasingly recognized as a key component of complex trait genetics.

Purpose of the Study:

• To investigate the genetic basis of alcohol preference by examining brain gene expression across generations of selected mouse lines.
• To identify genomic regions (eQTLs) that regulate gene expression related to alcohol consumption.
• To pinpoint overlapping genomic regions influencing both gene expression and alcohol preference phenotypes.

Main Methods:

• Utilized high and low alcohol-preferring (HAP3 and LAP3) mouse lines selected over generations.
• Performed quantitative trait locus (QTL) analysis to map genomic regions associated with alcohol preference.
• Analyzed brain gene expression to identify differentially expressed genes (de eQTLs) and genes with reduced expression variance (rv eQTLs).

Main Results:

• Identified specific genomic regions controlling the expression of genes associated with alcohol preference.
• Found overlapping regions between de eQTLs, rv eQTLs, and phenotypic QTLs, indicating selection impact.
• These overlapping regions harbor candidate genes critical for the predisposition to alcohol consumption differences.

Conclusions:

• Genomic regions identified through overlapping eQTL and QTL analyses are significantly affected by selection for alcohol preference.
• These regions regulate the expression of candidate genes that underlie innate differences in alcohol consumption.
• This study provides a framework for understanding the genetic architecture of complex behaviors like alcohol preference.