Genetic Determinants of Disease Trajectory in Sarcoidosis

In a Swedish cohort of 1,515 sarcoidosis cases, chronicity-linked genetics were identified, including rs3135356 for Lofgren’s syndrome nonchronic (OR=3.13, 95% CI 2.38–4.12).

• Why it matters: Sarcoidosis shows distinct clinical trajectories, but the genetic basis of chronic versus nonchronic phenotypes remains unclear, limiting precision risk stratification and treatment planning.
• What they did: Clinicians classified chronicity over 2 years, then Immunochip genotyping was analyzed in 1,515 Swedish cases versus 3,085 controls, with replication in 1,216 German cases versus 3,042 controls. Meta-analysis used inverse variance weighting (p<5e-8), followed by gene-based, enrichment, and pathway analyses.
• The result: Gene-based results linked CLIC1 to nonchronic forms and ANXA11 to the chronic phenotype, while enrichment implicated immune-cell/whole-blood/lung eQTLs and pathway analysis highlighted antigen presentation.

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