Center for Genetics, Genomics, and Epigenetics of Substance Use Disorders in Outbred Rats

Project Summary (Overall) The goal of this P30 application is to support the community of scientists who use outbred heterogeneous stock (HS) rats to understand the genetic basis of individual differences in vulnerability to substance use disorders (SUDs). Although this is a new grant, one of its main goals is to provide core services

that have been offered for the past 10-years by our NIDA P50 grant. When that grant was originally funded, mice were the mainstay of mammalian quantitative genetics. A major study using HS rats had recently been completed in Europe, and Dr. Leah Solberg Woods (PI of Core B) was maintaining the only US-based colony

of HS rats, which was supported by an R01 from NIDDK. A central theme of our initial P50 was that establishing the HS rat as a platform for quantitative genetic studies would allow us to examine complex behavioral traits that were difficult or impossible to study in mice. Ten years later, we have established a vibrant

community of investigators who use HS rats not only for genome wide association studies (GWAS) but also to study the genetic basis of individual differences in vulnerability to SUD-like behaviors. We have also accumulated a database of more than 15,000 deeply phenotyped and genotyped rats. This community

depends on several critical core services that will be provided by this P30. First, and foremost, Core B, the Breeding Core, will maintain two HS rat breeding colonies, located at Wake Forest University and the University of California San Diego. An innovative new component of Core B is our introduction of RATTACA,

which uses data collected over the last decade to predict phenotypes of newborn HS rats based on their genotype. As we describe, RATTACA allows us to provide groups of rats with high and low phenotypes, allowing non-geneticists to study individual differences using statistically valid methodology. Core C, the

Genotyping, Analysis and eQTL Core, provides services including genotyping of HS rats, GWAS, mapping of expression quantitative trait loci (eQTLs), and transcriptome wide association studies (TWAS). In addition, the Administrative Core (Core A), will maintain and distribute data from more than 15,000 HS rats that have

been accumulated over the last decade, as well as newly collected data, following FAIR (Findable, Accessible, Interoperable, and Reusable) practices as described in our Data Management and Sharing Plan. The Administrative Core will also provide oversight, coordination, education for high school and undergraduate

students and will implement several aspects of our Plan for Enhancing Diverse Perspectives (PEDP). Finally, Core D, the Pilot Project Core, will provide grants and free services from Cores A, B and C in an effort to support early-stage investigators, broaden the impact of our center, and execute our PEDP. These

cores will provide both stability and innovation that will promote the use of HS rats to study the genetic basis of individual differences.