The project will aim to link maternal diet to psychiatric disease using mouse models and specially designed statistical methods. The fields of mouse genetics, behavior genetics, and statistical modeling will all play a role in the study.
In the NIH summary statement, the reviewers gave the proposal an impact score of 10, corresponding to the 1st percentile, the top score possible for a grant application. The summary also highlighted the project’s “potential to have a huge impact on the field by changing how we think about environment and how it can affect risk for psychiatric disorders through in utero exposure, maternal diet and parent-of-origin effects.”
“There are clearly both genetic and environmental components in the risk for developing psychiatric disorders, but studying these in detail is difficult in human populations,” said Tarantino. “Mouse models allow us to control both the genetics and environment, and study behavioral changes in assays that model anxiety and depression. It is our hope that this work will lead to the identification of specific genes and processes that mediate the interaction between the environment and the genome to increase risk for these devastating disorders.”
“The way that multiple risk factors combine to affect disease susceptibility can be highly complex,” said Valdar. “Experimental systems such as mice can help us figure out those relationships, varying some genes and environmental factors while holding others constant.”
Asked why statistical modeling is important for the project, Valdar added, “Asking complicated questions in a focused way requires making good decisions about how to design, analyze and interpret experiments, and often those decisions are not at all obvious at the start. This is where good statistical modeling shines….Good statistical modeling, whether in baseball, electoral polling, or biomedical science, helps us identify systematic effects on an outcome and make informed choices about what to do next.”
The study will utilize resources from the Collaborative Cross, and success is dependent on highly trained staff. The grant money will not only pay for experiments but also help fund graduate students and postdoctoral fellows to study behavior, develop tailored modeling strategies, and analyze data to determine best next steps for future experiments.
After a year and a half of effort designing the study, Tarantino, Valdar and Fernando are elated that the NIMH funded the project. “We are immensely relieved, grateful to the anonymous expert reviewers for taking the time to recognize the study’s potential, and grateful to the University, School of Medicine, our departments and the Lineberger Comprehensive Cancer Center for helping to support us in the run-up,” said Valdar. “Most of all, we are excited to be finally starting the project!”