This center began in 2014 as the National Institute for Drug Abuse (NIDA) National Center of Excellence for GWAS in Outbred Rats, and was renewed in 2019 as the Center for Genetic Studies of Drug Abuse in Outbred Rats (P50DA037844); in 2024 we transitioned to the current P30 center, the Center for Genetics, Genomics, and Epigenetics of Substance Use Disorders in Outbred Rats, which is funded by NIDA until 2029 (P30DA060810).
What does the Center do?
The goal of this Center is to support the use of heterogeneous stock (HS) rats for studying the genetic basis of individual differences across a wide range of behaviors relevant to substance use disorders (SUDs).
HS rats were created in 1984 by interbreeding 8 inbred rat strains, and have now been maintained as an outbred population for almost 100 generations (see Core B). This means that the founder chromosomes have been broken into small fragments by recombination, making them ideal for genome-wide association studies (GWAS). Since 2014 the Center has created a multidisciplinary community of investigators who use GWAS and other quantitative genetic techniques to study SUD-relevant behaviors. GWAS studies include self-administration of cocaine, oxycodone, heroin, nicotine and alcohol, as well as measures of impulsivity, attention, learning, and numerous other SUD-relevant traits. In addition to GWAS, bulk and single cell transcriptomics and epigenetics and slice electrophysiology are now being applied to understand the genetic basis of individual differences at many levels of analysis. As a P30 Center, we continue to support and expand this dynamic community.
The Center provides several critical core services.
The Breeding Core maintains the only HS rat breeding colony in the world. In addition to providing HS rats from the general colony, we introduce a novel concept of RATTACA (RAT Trait Ascertainment using Common Alleles), which uses genetic data in >20,000 HS rats that has been collected over the last decade to predict the phenotypes of newborn HS rats. RATTACA allows us to identify groups of rats likely to display high and low phenotypes, which will allow addiction neuroscientists to use our sophisticated quantitative genetics approaches to address fundamental questions about individual differences using simple two-group comparisons.
The Genotyping, Analysis and eQTL Core (Core C) provides economical and highly accurate genotyping of HS rats, GWAS and related analyses, mapping of expression quantitative trait loci (eQTLs), and transcriptome wide association study (TWAS), which identifies correlations between genetically estimated gene expression and all of the traits that have been studied in our database.
The Administrative Core (Core A) coordinated Center’s activities. This Core maintains data according to FAIR (Findable, Accessible, Interoperable, and Reusable) practices and in compliance with our Data Management and Sharing Plan. It distributes data to collaborators, including machine learning researchers. Core A also provides educational opportunities including Research Experiences for High School and Undergraduate Students (REHU) and implements Plan for Enhancing Diverse Perspectives (PEDP).
The Pilot Project Core (Core D) provides pilot project grants and free services from Cores A, B and C to support early-stage investigators, broaden the impact of our center, and implement our PEDP.
[Contact [email protected] for more information about the P30 Center.]
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