Genome-wide association study of delay discounting in Heterogeneous Stock rats
Montana Kay Lara1, Apurva S Chitre1, Denghui Chen1
1Department of Psychiatry, University of California San Diego, La Jolla, California, USA.
Genes, Brain, and Behavior
|August 9, 2024
Summary
This study identified novel genes linked to delay discounting, a behavior associated with addiction. Genetic variations in Slc35f1 and Adgrl3 influence how individuals value immediate versus delayed rewards.
Area of Science:
- Behavioral Neuroscience
- Genetics
- Psychopharmacology
Background:
- Delay discounting, the devaluation of rewards with delay, is linked to substance use disorders and other psychopathologies.
- While heritable, the specific genes influencing delay discounting remain largely unknown.
- Genome-wide association studies (GWAS) are crucial for identifying genetic underpinnings of complex behaviors.
Purpose of the Study:
- To identify novel genetic loci associated with delay discounting behavior.
- To utilize a genetically diverse rat model (Heterogeneous Stock rats) for comprehensive genetic analysis.
- To investigate the genetic architecture of reward valuation and impulsivity.
Main Methods:
- A genome-wide association study (GWAS) was conducted on 650 Heterogeneous Stock rats.
- Delay discounting was assessed using an adjusting amount procedure with sucrose rewards.
- Genetic loci were identified by analyzing preference switch points, area under the curve (AUC), and the discounting parameter k.
Main Results:
- Significant genetic loci associated with delay discounting were identified on chromosomes 20 and 14.
- The solute carrier family gene Slc35f1 was located within the chromosome 20 locus, with evidence of an expression quantitative trait locus (eQTL).
- The latrophilin subfamily G-protein coupled receptor gene Adgrl3 was identified within the chromosome 14 locus.
Conclusions:
- Novel genes, Slc35f1 and Adgrl3, are implicated in the heritability of delay discounting.
- These findings suggest that genetic variations, potentially in gene expression, contribute to individual differences in reward valuation.
- Further research is warranted to explore the functional roles of these genes in behavior and addiction vulnerability.
