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.