IP: Dra. Gemma Rojo Martínez

Resumen del proyecto: Complete genomic sequences will become increasingly accessible, but more studies are needed to demonstrate their usefulness in common diseases such as type 2 diabetes (T2D). T2D affects >10% of the Spanish adult population, and is one of the leading causes of mortality and health expenditure. It is extremely heterogeneous, but lacks markers to guide personalized therapeutic decisions. Polygenic risk scores (PRS) have the potential to discriminate different risk mechanisms for T2D. On the other hand, it is known that a small set of patients have coding mutations capable of guiding clinical decisions, and 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, complete genomes will be obtained from a unique cohort of 1000 patients with a T2D subphenotype that maximizes genetic load. You will define partitioned PRS and causal rare variants, and use AI tools to develop stratification models. It will generate a second validation cohort, with broader phenotypic criteria, using genotyping panels. With it, you will validate stratification models, and study differences in pharmacological responses at extremes of the polygenic spectrum. Finally, it will develop mechanisms to implement this knowledge in the health system. ImpactT2D is aligned with precision medicine and genomics initiatives in T2D in Spanish and international healthcare centers. It leverages a network of primary care, clinical investigators, 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 contribute transformative findings for precision medicine in T2D.

Entidad financiadora: The ISC III