Full Title: ImpactT2D: A genomic strategy for implementing precision medicine in type 2 diabetes

Funded by: Instituto de Salud Carlos III (PMP21/00069)

Grant awarded: €140,855.00

Duration: 4 years (01/01/2022-31/12/2025)

Principal Investigator: Ana María Wägner

Associated Researchers: Nicolás Martel Suarez, Begoña Vega Guedes, Lidia García Pérez, Yolanda Ramallo Fariña, Cristina Valcárcel Nazco, Yeray Brito Casillas, Verónica Dávila Batista, Ana María González Lleo, María del Carmen Valverde Tercedor, Alejandro Déniz García, Dulce Hernández Correa

Objectives and Methodology

Whole genome sequences are becoming increasingly accessible, yet more studies are needed to demonstrate their utility in common diseases like type 2 diabetes (T2D). T2D affects approximately 14% of the Spanish adult population and is a leading cause of mortality and healthcare expenditure. It is extremely heterogeneous but lacks markers to guide personalized therapeutic decisions. Polygenic risk scores (PRS) have the potential to discriminate between different mechanisms of risk for T2D. Additionally, a small group of patients harbors coding mutations that can guide clinical decisions. The DecodeDiabetes study has identified non-coding mutations shared by patients with monogenic diabetes and T2D. ImpactT2D will deploy a strategy to demonstrate the clinical applicability of genomic information in T2D.

To this end, it will obtain complete genomes from a unique cohort of 1,000 patients with a T2D subphenotype that maximizes genetic burden. It will define partitioned PRS and rare causal variants, and use AI tools to develop stratification models. A second validation cohort will be generated with broader phenotypic criteria using genotyping panels. This cohort will be used to validate stratification models and study differences in pharmacological responses at the extremes of the polygenic spectrum. Finally, mechanisms will be developed to implement these findings into the healthcare system.

ImpactT2D aligns with precision medicine and genomic initiatives in T2D across Spanish and international healthcare centers. It leverages a network of primary care, clinical researchers, clinical and genomic cohorts directly relevant to the project, as well as multidisciplinary expertise in AI, clinical trials, genomics, and genetics. The strategy aims to provide transformative insights for precision medicine in T2D.

Contact Person: Ana María Wägner