Genetic and Lifestyle Factors Linked to Sarcoidosis Risk

A new genome-wide association study (GWAS) identifies 28 genetic loci, modifiable risk factors, and circulating biomarkers associated with sarcoidosis.

A large-scale GWAS involving 9,755 sarcoidosis cases and over 1.5 million controls has pinpointed key genetic risk factors for the disease. The strongest association was found at the C1orf141-IL23R locus, with additional risk loci linked to immune system genes such as TYK2, ANXA11, CCDC88B, and IL23R. Gene expression studies highlighted sarcoidosis-related activity in the spleen, whole blood, and lungs, with key pathways involving T cell activation, leukocyte adhesion, and cytokine signaling.

Mendelian randomization analysis also revealed modifiable risk factors. Higher body mass index (BMI) was associated with increased sarcoidosis risk, while moderate-to-vigorous physical activity (MVPA) was linked to a lower risk. Notably, circulating levels of interleukin-23 receptor (IL23R) and eight inflammatory proteins were significantly correlated with disease susceptibility.

These findings reinforce sarcoidosis’ genetic and immune-mediated nature and suggest potential therapeutic targets, particularly IL23R and TYK2, which are already under investigation for other autoimmune conditions.

Citation

Yuan, S., Chen, J., Geng, J. et al. GWAS identifies genetic loci, lifestyle factors and circulating biomarkers that are risk factors for sarcoidosis. Nat Commun 16, 2481 (2025). https://doi.org/10.1038/s41467-025-57829-z