Discovery of clinical biomarkers in organ-specific sarcoidosis phenotypes via the integration of genome, transcriptome, and methylome coupled with lifestyle and environmental exposures

Bakgrund:

Sarcoidosis is a systemic inflammatory and granulomatous disease of unknown etiology that affects any organ in the body; however, the lung is mostly affected. Evidence suggests that the genetic architecture of sarcoidosis is specific to target-organ, and therefore the disease architecture for each affected organ varies. At present, no biomarker can distinguish between sarcoidosis phenotypes or foretell the course of the disease.

Målsättning:

In order to determine the genetic architecture of target-organ sarcoidosis, mainly pulmonary, cardiac, skin, and ocular sarcoidosis, as well as chronic and resolving phenotypes, we will carry out genomic investigations using various cohorts available in the MESARGEN consortium.

Our goal is to identify molecular biomarkers and determine genomic signatures of target-organ sarcoidosis phenotypes via the integration of meta-genomic data coupled with lifestyle and environmental exposures. Arbetsplan:

Using eight population-based cohorts, totaling 7,500 individuals a compendium of genomic data, i.e., a meta-analysis of genome-wide association studies, DNA-methylation studies, and transcriptome-wide association studies will be conducted in target-organ phenotypes. We will also integrate the genomic data with lifestyle and environmental factors, thus to identify genomic signatures that can classify individuals susceptible to the disease and those with an increased risk for adverse outcomes.

Betydelse:

The significance of this work includes a) dissecting the genetic architecture of sarcoidosis target-organ phenotypes that can lead to better diagnostic and prognostic tools and implementation of new treatments; (b) discovery of biomarkers that can be used in the clinic to identify affected individuals and predict disease course; and (c) an innovative paradigm platform that may serve for investigation other lung diseases, e.g., asthma, COPD, pulmonary fibrosis.