Point mutations and complex variants impact gene expression and addiction-related behaviors in Heterogeneous Stock rats
Year: 2026
Type: preprint
Abstract: Summary While various variants, including single nucleotide polymorphisms ( SNPs ), small insertions/deletions, short tandem repeats and structural variants, drive individual genetic differences, their influence on gene expression and complex traits remains unclear. We used short- and long-read sequencing to generate a comprehensive variant catalog in Heterogeneous Stock ( HS ) rats and performed joint cis-expression quantitative trait loci ( cis-eQTL ) mapping across five brain regions. We found that non-SNP variants accounted for over 50% of lead regulatory associations, many of which were poorly tagged by nearby SNPs using linkage disequilibrium ( LD ). Comparison between joint and SNP-only analyses showed that over 46% of shared eQTL genes had a non-SNP lead cis-eQTL, and fewer than half were in strong LD with the corresponding lead eSNP. Linking joint cis-eQTLs to complex trait associations identified mechanisms missed by SNP-only approaches, highlighting the importance of incorporating diverse variant types into genetic studies and providing a foundational resource for the HS rat community.
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: Center for Genetic Studies of Drug Abuse in Outbred Rats, Center for Genetics, Genomics, and Epigenetics of Substance Use Disorders in Outbred Rats, Characterization of Tandem Repeat and Structural Variants Contributing to Addictive Behaviors in Mice and Rats, Unraveling the Role of Tandem Repeats and Structural Variants in Addiction-Related Behaviors Using Heterogeneous Stock Rats
OpenAlex ID: W7213286532