# The role of structural variants and tandem repeats in substance abuse-related behavioral traits > **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $58,435 ## Abstract Project Summary Genome-wide association studies (GWAS) in model organisms such as mice and rats have identified hundreds of genetic loci that are associated with addictive behaviors, but determining the causal genes remains challenging. Single nucleotide polymorphisms (SNPs) may not adequately tag other classes of variants such as structural and repetitive variants that have higher mutation rates. Thus, both panels of inbred strains and outbred populations will fail to identify a subset of loci and causal alleles. We are proposing to address this serious limitation by using cutting-edge methods to discover and genotype structural variants (SVs) and tandem repeats (TRs). Because they are technically challenging to analyze, SVs and TRs have not yet been adequately surveyed in rodents. However, there is already extensive evidence that SVs and TRs are prevalent in mice and rats, and that they have important functional consequences. Our proposal brings together complementary expertise in human genetics and bioinformatic analysis of SVs (Sebat) and repetitive variation (Gymrek) with established leadership in elucidating the genetic basis of behavioral phenotypes in model organisms (Palmer). This study will generate the first large-scale resource for analyzing the effects of complex variation on mouse and rat phenotypes. We use this resource to examine gene expression and behavioral traits in inbred mice (BXD recombinant inbred strains, the Hybrid Mouse Diversity Panel (HMDP), the Diversity Outbred (DO) mice, the Hybrid Rat Diversity Panel (HRDP) and the Heterogeneous Stock (HS) outbred rats. In Specific Aim 1 we will characterize SVs in inbred and outbred mice and rats by single-molecule sequencing. In Specific Aim 2 we will genotype TR in inbred and outbred mice and rats. Finally, in Specific Aim 3 we will perform GWAS using SV and TR for gene expression and behavioral traits. We will determine the phenotypic consequences of the SV and TR genotypes on gene expression and behavioral traits. We will impute SVs and TRs into outbred mice and rats and then perform GWAS using the wealth of preexisting gene expression and behavioral data that are available for the mouse and rat populations studied in this project. Completion of this project will characterize the SV and TR landscape in mice and rats, elucidate their role in gene expression and complex behavioral traits relevant to addiction, and create a community resource that will enhance numerous ongoing mouse and rat genetic studies. In this supplement request, we are extending on the studies funded by the parent grant to pursue a new line of genetic analysis using the datasets produced by Aims 1 and 2. Specifically, we will calculate polygenic risk scores (PRS) from GWAS summary statistics and determine if PRS modifies the effects of damaging large effect SVs and TRs that are discovered by the parent grant. ## Key facts - **NIH application ID:** 10838864 - **Project number:** 3U01DA051234-03S1 - **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO - **Principal Investigator:** Melissa Gymrek - **Activity code:** U01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2023 - **Award amount:** $58,435 - **Award type:** 3 - **Project period:** 2021-05-01 → 2025-08-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10838864 ## Citation > US National Institutes of Health, RePORTER application 10838864, The role of structural variants and tandem repeats in substance abuse-related behavioral traits (3U01DA051234-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10838864. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*