NWO has awarded Danielle Posthuma a Vici-grant of 1.5 million Euro to conduct research over the next five years.
Prof. D. (Danielle) Posthuma, CNCR, Group Leader
“This VICI grant allows me to develop novel statistical tools to increase the detection of genetic risk variants for psychiatric traits, and also to strengthen my collaboration with functional biologists. We have designed a novel, strong paradigm that has the potential to identify cellular mechanisms underlying psychiatric traits, such as schizophrenia. I am very excited to be able to start this project!”
Novel polygenic models for mental disorders: from risk detection to disease mechanism
Mental disorders are a major economic, societal and personal burden. Current treatments are seriously hampered by a lack of insight into disease mechanisms, while prevention strategies would greatly benefit from improved risk prediction models. After a century of limited etiological progress, the past decade has seen unprecedented advances in our understanding of the fundamental genetic architectures of mental disorders. It is now well established that mental disorders are highly polygenic. Over 130+ robust genetic risk variants have already been identified, and with increasing sample sizes, more will be detected soon. To benefit from this wealth of genetic findings, the principal challenge for the near future is to address the highly polygenic nature of mental disorders. Current methods for 1) gene detection, 2) genetic risk prediction, and 3) functional validation insufficiently address this challenge, as they predominantly rely on assessing the effect of single risk variants independent of other variants, often neglecting the concerted action of genes.
Danielle Posthuma said the following:
“Using my past experience in statistical genetics and integrating biological information with human genetics, I propose to develop novel and improved methods for the above three issues. Key to this proposal is the focus on the concerted effects of multiple genetic factors and the adoption of innovative methods to investigate the cellular function of hundreds of genetic factors at the same time. I will capitalize on the immense efforts of the international Psychiatric Genomics Consortium by using their most recent and largest datasets for application to mental disorders. For functional validation of genetic findings I will strongly collaborate with the NCA-stem cell lab and conduct biological experiments that appropriately account for multiple genetic risk variants. The overarching goal of my proposal is to identify disease mechanisms for mental disorders. This proposal is highly timely as we now have well-powered datasets and biological information that urgently needs to be incorporated into our disease models. The results of the proposed research will aid in identifying novel targets for treatment and will greatly impact early prevention strategies for mental disorders.”