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Semin Respir Crit Care Med
DOI: 10.1055/a-2741-2120
Review Article

Genetics in Sarcoidosis and Its Burden as a Multisystem Disease

Authors

  • Natalia V. Rivera 

    1   Division of Immunology and Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden

  • Anders Eklund

    1   Division of Immunology and Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
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Abstract

Sarcoidosis is a complex, immune-mediated disease characterized by a broad spectrum of clinical and molecular phenotypes—often referred to as endophenotypes—some of which progress to chronic outcomes such as pulmonary fibrosis. Despite decades of research, the pathogenesis of sarcoidosis remains incompletely understood, primarily due to its clinical heterogeneity and the absence of robust preclinical models. Established risk factors include age, sex, ethnicity, geographic origin, and environmental exposures, all of which contribute to granuloma formation and the activation of profibrotic pathways. These inflammatory cascades promote fibroblast proliferation and aberrant tissue remodeling, ultimately leading to interstitial lung pathology and fibrosis. A central feature of sarcoidosis is the dysregulation of immune regulatory mechanisms, likely driven by genetic susceptibility and immune dysfunction. Understanding the genetic architecture of sarcoidosis is crucial for identifying the molecular drivers of the disease, discovering biomarkers for early diagnosis and prognosis, and developing targeted therapies. This review synthesizes current knowledge on the genetic and genomic landscape of sarcoidosis, highlighting key loci and biological pathways implicated in disease susceptibility and progression.

Keywords

genetics - single-nucleotide polymorphisms - GWAS - human leukocyte antigen - MHC

Contributors' Statement

N.V.R. contributed in study design and writing. All authors read and approved the final manuscript.




Publication History

Received: 10 October 2025

Accepted: 06 November 2025

Article published online:
24 November 2025

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