Genome-wide association study of delay discounting in Heterogenous Stock rats

Area of Science:

• Behavioral neuroscience
• Genetics
• Psychopharmacology

Background:

• Delay discounting, the devaluation of delayed rewards, is linked to substance use disorders and other psychopathologies.
• While delay discounting is heritable, specific genetic underpinnings remain largely unknown.
• Identifying these genes can offer insights into addiction and related conditions.

Approach:

• A genome-wide association study (GWAS) was conducted in Heterogenous Stock rats, a genetically diverse population.
• Delay discounting behavior was assessed using an adjusting amount procedure, measuring choices between immediate and delayed rewards.
• Genetic loci associated with delay discounting measures (AUC, k parameter) were identified.

Key Points:

• Significant genetic loci for delay discounting were found on chromosomes 20 and 14.
• The solute carrier family gene Slc35f1 on chromosome 20 was identified, with evidence of an expression quantitative trait locus (eQTL).
• The latrophilin family gene Adgrl3 on chromosome 14 was also implicated.

Conclusions:

• This research identifies novel genes, Slc35f1 and Adgrl3, associated with delay discounting behavior.
• These findings contribute to understanding the genetic architecture of decision-making under delay.
• Further research is warranted to explore the functional roles of these genes in behavior.