WP3

Genetic Diagnosis and Biomarkers

As illustrated by the presence of a familial form in 15% of pulmonary fibrosis cases, the genetic background is a major factor in the pathophysiology of pulmonary fibrosis, from birth to adulthood.

Description and Mission

Interestingly, the genes involved are primarily expressed in epithelial cells, and among them, certain inflammation-related genes (e.g., TNFRSF6B, STING) are identified as risk factors for pulmonary fibrosis, particularly in patients suffering from inflammatory rheumatism.

In addition, the genetic causes of Marfan syndrome or cardiac amyloidosis highlight the importance of pathological cardiovascular remodeling.

Identifying the links between these genes, inflammation, the development of fibrosis, as well as their interaction with the genetic causes of cardiac channelopathies, from birth to adulthood, will be a major objective of this project. This will not only allow for a better understanding of these rare diseases but also to identify key mechanisms common to several pathologies.

We will rely on the already established cohorts and the cross-expertise of the FHU teams to create harmonized research procedures, fostering mutual benefits between teams.

Analyses will include:

A better description of genotype/phenotype correlations from childhood to adulthood, with cluster analysis by disease and by organ;
The identification of new rare germline variants responsible for diseases managed by our centers;
Analysis of common germline variants and their interactions with rare variants;
An analysis of somatic variants, in blood or organs, by organ, compared to phenotypic and germline genotypic data;
Finally, these data will be correlated with environmental exposures for individualized risk assessment.

All of these data will directly feed into WP4.