Sarcoidosis affects all ancestries, underscoring its global prevalence.

Sarcoidosis is immunologically driven, with HLA-DRB1 present across its endotypes.

Genetic studies shall address sarcoidosis heterogeneity via collaborative efforts.

Endophenotype associations can be attributed to ancestry or environment.

Sarcoidosis shares genetic and molecular features with autoimmune diseases.

Sarcoidosis is a complex, polygenic, and multifactorial disease characterized by granulomas in affected organs, which are the hallmark of the condition. Genetic susceptibility, environmental influences, and lifestyle factors play key roles in its development. Although the exact molecular mechanisms are not yet fully understood, it is known that the immune system plays a role in mediating the disease. Additionally, sarcoidosis encompasses a group of disease entities (endophenotypes) whose clinical features and progression can be described to help improve understanding of their genetic architecture. In this work, we aim to review recent advances in the genetics and immunopathogenesis of sarcoidosis and explore future directions to improve clinical outcomes and achieve the goals of precision medicine.

© 2025 The Author(s). Published by Elsevier Ltd.