An inflammatory disease of unknown cause that forms tiny clusters of immune cells in organs, most often the lungs — a 2016 fine-mapping study found its genetics concentrate overwhelmingly in the MHC region, and differ measurably between its two main clinical presentations.
Sarcoidosis is a multisystem inflammatory disease of unknown cause, most often affecting the lungs, in which the immune system forms small clusters of inflammatory cells called granulomas. Löfgren's syndrome (LS) is a distinct, acute-onset subgroup — associated with a notably better prognosis — while non-Löfgren's sarcoidosis describes the broader, more variable presentation.
Rivera et al. 2016 genotyped a Swedish discovery cohort of 384 people with Löfgren's syndrome, 664 with non-Löfgren's sarcoidosis, and 2,086 controls, using a dense fine-mapping array, then replicated the findings in 7,766 more people across four independent cohorts. The genetics turned out to concentrate overwhelmingly in one place: 727 variants associated with Löfgren's syndrome across the extended MHC region, and 68 variants associated with non-Löfgren's sarcoidosis specifically within the MHC class II region. 17 variants were shared between both subtypes.
The six variants on this page — rs13213152 (ZKSCAN3), rs3129788 (OR2B3P), rs1233491 (MAS1L), rs8321 (ZNRD1), rs389884 (STK19) and rs11244 (HLA-DOB) — all map to genes within or immediately beside the MHC region, consistent with where the great majority of this study's confirmed associations sit. Each reached genome-wide significance in its own right (p-values from 4×10⁻¹¹ to 1×10⁻³²).
Outside the MHC, the study found only two confirmed Löfgren's-specific loci, in ADCY3 and between CSMD1 and MCPH1 — neither is on this page. That contrast is itself a finding: sarcoidosis genetics, at least as this study measured it, is concentrated in immune-recognition genes almost to the exclusion of everywhere else in the genome.
2025-12-29 · Genome-wide association for sarcoidosis identifies novel risk loci and genetic heritability in African and European ancestries: a meta-analysis from the FinnGen, Million Veteran Program, UK Biobank, and Biobank Japan datasets. Orphanet Journal of Rare Diseases. 2025. DOI:10.1186/s13023-025-04097-1
Sarcoidosis is a rare inflammatory disease that forms characteristic immune granulomas, and this study combined summary statistics from FinnGen, UK Biobank, the Million Veteran Program and Biobank Japan for the largest multi-ancestry sarcoidosis genetics analysis to date: 9,659 cases (7,559 European, 1,880 African, 220 East Asian) against 1,665,804 controls. It found 19 risk loci in European ancestry and 2 in African ancestry, with SNP-based heritability estimated at 0.25 (European) and 0.19 (African) -- a moderate, comparable genetic contribution across both groups. Candidate genes flagged for functional follow-up (outside the MHC region) included IL23R, PUS10, ACOXL, PLCL1, FAM117B, BMPR2, PPARG, ESYT2, ANXA11, CCDC88B, ATXN2, CCL24, HOMER2, CD19, UBASH3A and RNF215. IL23R is notable as a well-known inflammatory bowel disease gene, and CD19/UBASH3A point toward B-cell and T-cell regulatory pathways respectively -- enrichment analysis specifically flagged interferon gamma signaling as a key pathway, consistent with sarcoidosis's granuloma-forming immune biology. A separate confirmatory meta-analysis (FinnGen+UKBB+MVP alone) found 18 consistent risk loci, supporting the robustness of the main findings. This site's sarcoidosis page carries 7 variants; none of these newly reported genes are currently among them.
Sarcoidosis is diagnosed by imaging, biopsy showing granulomas, and ruling out other causes — not by genotype. None of the 6 variants on this page are used by any guideline to diagnose sarcoidosis or distinguish Löfgren's from non-Löfgren's disease in an individual.
The scale of MHC-region involvement found here (nearly 800 variants across both subtypes combined) is itself a population-level pattern from thousands of people, not an individual test — but it is a striking illustration of how concentrated in one genomic region a whole disease's genetics can be.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Sarcoidosis comes down to these specific, well-studied positions — not a diagnosis.
HLA-DOB · rs11244
See detailed info →MAS1L · rs1233491
See detailed info →ZKSCAN3 · rs13213152
See detailed info →OR2B3P · rs3129788
See detailed info →STK19 · rs389884
See detailed info →ZNRD1 · rs8321
See detailed info →The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 7 of 7 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
Sarcoidosis is an inflammatory disease of unknown cause in which the immune system forms small clusters of cells called granulomas, most often in the lungs. Löfgren's syndrome is a distinct, better-prognosis subgroup; non-Löfgren's sarcoidosis is the broader presentation.
Studying 3,134 people directly and replicating in 7,766 more, it found 727 variants associated with Löfgren's syndrome and 68 with non-Löfgren's sarcoidosis, nearly all within the MHC region, with only two confirmed loci found entirely outside it.
Not from what this page can independently confirm. The underlying journal article is not freely accessible, so while GWAS Catalog confirms genome-wide significance for these variants against sarcoidosis broadly, this page does not assert which specific subtype each belongs to.
No. Sarcoidosis is diagnosed by imaging and biopsy, not genotype. This is a population-level finding from thousands of people, not an individual diagnostic test.
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