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The regulatory landscape of multiple brain regions in outbred heterogeneous stock rats

View ORCID ProfileDaniel Munro, View ORCID ProfileTengfei Wang, View ORCID ProfileApurva S Chitre, View ORCID ProfileOksana Polesskaya, View ORCID ProfileNava Ehsan, Jianjun Gao, View ORCID ProfileAlexander Gusev, View ORCID ProfileLeah C Solberg Woods, View ORCID ProfileLaura M Saba, View ORCID ProfileHao Chen, View ORCID ProfileAbraham A Palmer, View ORCID ProfilePejman Mohammadi
doi: https://doi.org/10.1101/2022.04.07.487560
Daniel Munro
1Department of Psychiatry, University of California San Diego, La Jolla, CA
2Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA
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Tengfei Wang
3Department of Pharmacology, Addiction Science and Toxicology, University of Tennessee Health Science Center, Memphis, TN
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Apurva S Chitre
1Department of Psychiatry, University of California San Diego, La Jolla, CA
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Oksana Polesskaya
1Department of Psychiatry, University of California San Diego, La Jolla, CA
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Nava Ehsan
2Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA
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Jianjun Gao
1Department of Psychiatry, University of California San Diego, La Jolla, CA
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Alexander Gusev
4Division of Population sciences, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
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Leah C Solberg Woods
5Wake Forest University School of Medicine, Department of Internal Medicine, Section on Molecular Medicine, Winston Salem, NC
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  • ORCID record for Leah C Solberg Woods
Laura M Saba
6Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO
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  • ORCID record for Laura M Saba
Hao Chen
3Department of Pharmacology, Addiction Science and Toxicology, University of Tennessee Health Science Center, Memphis, TN
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Abraham A Palmer
1Department of Psychiatry, University of California San Diego, La Jolla, CA
7Institute for Genomic Medicine, University of California San Diego, La Jolla, CA
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  • For correspondence: pejman@scripps.edu
Pejman Mohammadi
2Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA
8Scripps Research Translational Institute, Scripps Research, La Jolla, CA
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  • For correspondence: pejman@scripps.edu
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Abstract

Heterogeneous Stock (HS) rats are a genetically diverse outbred rat population that is widely used for studying genetics of behavioral and physiological traits. Mapping Quantitative Trait Loci (QTL) associated with transcriptional changes would help to identify mechanisms underlying these traits. We generated genotype and transcriptome data for five brain regions from 88 HS rats. We identified 21,392 cis-QTLs associated with expression and splicing changes across all five brain regions. Surprisingly, use of a linear mixed model had little impact on the eQTLs identified compared to linear regression. We also characterized empirical properties of these QTLs and validated their effects using allele specific expression data. We identified 80 cases where eQTLs were colocalized with GWAS results from nine physiological traits, demonstrating the utility of these eQTL data. Comparing our dataset to human data from the Genotype-Tissue Expression (GTEx) project, we found that the HS rat data yields twice as many significant eQTLs as a similarly sized human dataset. We also identified a modest but highly significant correlation between genetic regulatory variation among orthologous genes. Surprisingly, we found less genetic variation in gene regulation in HS rats relative to humans, though we still found eQTLs for the orthologs of many human genes for which eQTLs had not been found. These data are available from the RatGTEx data portal (RatGTEx.org) and will enable new discoveries of the genetic influences of complex traits.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://ratgtex.org/

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted April 09, 2022.
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The regulatory landscape of multiple brain regions in outbred heterogeneous stock rats
Daniel Munro, Tengfei Wang, Apurva S Chitre, Oksana Polesskaya, Nava Ehsan, Jianjun Gao, Alexander Gusev, Leah C Solberg Woods, Laura M Saba, Hao Chen, Abraham A Palmer, Pejman Mohammadi
bioRxiv 2022.04.07.487560; doi: https://doi.org/10.1101/2022.04.07.487560
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The regulatory landscape of multiple brain regions in outbred heterogeneous stock rats
Daniel Munro, Tengfei Wang, Apurva S Chitre, Oksana Polesskaya, Nava Ehsan, Jianjun Gao, Alexander Gusev, Leah C Solberg Woods, Laura M Saba, Hao Chen, Abraham A Palmer, Pejman Mohammadi
bioRxiv 2022.04.07.487560; doi: https://doi.org/10.1101/2022.04.07.487560

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