Point mutations and complex variants impact gene expression and addiction-related behaviors in Heterogeneous Stock rats
- 1University of California San Diego
Abstract
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.
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BibTeX
@misc{chen2026point,
title = {{Point mutations and complex variants impact gene expression and addiction-related behaviors in Heterogeneous Stock rats}},
author = {D. Chen and K. A. Cohen and K.-M. H. Nguyen and H. Ziaei Jam and R. J. Eveloff and Y. Wang and J. Guevara and T. Missfeldt Sanches and M. Mortazavi and D. Munro and O. Polesskaya and J. L. Sebat and M. Gymrek and A. A. Palmer},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.10.750683},
url = {https://www.biorxiv.org/content/10.64898/2026.09.10.750683v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Point mutations and complex variants impact gene expression and addiction-related behaviors in Heterogeneous Stock rats
AU - D. Chen
AU - K. A. Cohen
AU - K.-M. H. Nguyen
AU - H. Ziaei Jam
AU - R. J. Eveloff
AU - Y. Wang
AU - J. Guevara
AU - T. Missfeldt Sanches
AU - M. Mortazavi
AU - D. Munro
AU - O. Polesskaya
AU - J. L. Sebat
AU - M. Gymrek
AU - A. A. Palmer
PY - 2026
DA - 2026/09/10
PB - bioRxiv
DO - 10.64898/2026.09.10.750683
UR - https://www.biorxiv.org/content/10.64898/2026.09.10.750683v1
AB - 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.
ER -