Research

Statistical Methods Development

One of the major challenges in developing accurate polygenic risk scores (PRS) is accounting for differences in risk among different ethnic and ancestral groups. Investigators in the CTG utilize the diverse BioMe biobank to develop statistical methods that are sensitive to different ancestries. Investigators in the CTG have deep expertise in the studies of genetic ancestry and population structure, and current and future lab members will be involved in combining this expertise with statistical methods for PRS development.

The Kenny Lab is also a contributing member of the Polygenic Risk Methods in Diverse Populations (PRIMED) Consortium, which is actively developing PRS methods for diverse ancestry populations. CTG will leverage cutting-edge advances made in the PRIMED Consortium to advance PRS development in clinical settings.

Standards Development

There are many different models available to calculate PRS, but there is little consensus on which models are most appropriate for predicting diseases or traits in clinical settings. Iterative development and testing of PRS across a range of clinical traits in the Mount Sinai health system will allow CTG to contribute to reporting on successful methods in clinical settings.

PRS Optimization and Validation

The CTG is committed to using current best practices in PRS generation, such as those developed by the O’Reilly Lab at Mount Sinai, to optimize and validate PRS using the diverse BioMe cohort. We are currently implementing the full Polygenic Score (PGS) Catalog in BioMe to investigate the accuracy of existing PRS in predicting traits and conditions among admixed populations.

Tool Development

The CTG leverages internal clinical informatics expertise to develop frameworks for new PRS clinical implementation tools, including but not limited to point-of-care risk prediction tools, conversational aids, and other clinical decision support tools.

The Kenny Lab is also an active contributor to the Electronic Medical Records and Genomics (eMERGE) Network, which is evaluating the clinical implementation of a Genome Informed Risk Assessment tool for selected conditions. Implementation tools developed within eMERGE and lessons learned from the Network will be highly valuable for informing the development of new tools and strategies within CTG.

Electronic Health Record Integration

The CTG develops strategies for integrating PRS tools within the Epic Electronic Health Record (EHR) system. This includes evaluating the extent to which the Epic genomics module can support PRS tools and developing strategies for linking available biobanks to the EHR system.

Clinical Interventions

The implementation of PRS in clinical practice is still in its infancy, and the clinical utility of PRS for individual clinical management is under active scrutiny. The CTG provides consultation services for developing clinical intervention trials for well-validated PRS that have potential clinical utility.

Potential interventions include:

• Risk stratification
• Patient education and communication
• Screening programs
• Prognosis estimates
• Health behavioral interventions

Outcomes Tracking

Investigators at the CTG advise collaborators on strategies for collecting clinical outcomes data to assess and refine PRS implementation.