An autoimmune disease that dries out the glands that make tears and saliva — a 2013 study of over 4,000 people found the strongest genetic signal ever measured in the condition, at the HLA region, alongside two more confirmed loci.
Sjögren's syndrome is an autoimmune disease, affecting an estimated 0.7% of European Americans, in which the immune system attacks the glands that produce tears and saliva. It typically presents as keratoconjunctivitis sicca (dry eyes) and xerostomia (dry mouth).
Lessard et al. 2013 combined four cohorts — 4,337 people with Sjögren's syndrome and 12,459 without — in what was, at the time, the largest genetic study of the condition. The single strongest result in the entire study was in the HLA class II region: rs115575857, near HLA-DQB1, reached a meta-analysis p-value of 7.65×10⁻¹¹⁴ — a level of statistical certainty rarely seen even in genome-wide studies.
Two more loci on this page were confirmed at genome-wide significance: rs17339836, in the IRF5-TNPO3 region (p=2.43×10⁻¹⁶), and rs6579837, near TNIP1 (p=3.30×10⁻⁸) — right at the genome-wide threshold, with 29 further variants in the same region showing suggestive but not confirmed association.
Across the individual cohorts in the study, odds ratios for these three positions ranged from roughly 1.6 to 3.3 — real effects, though the HLA association in particular reflects how strongly this immune-recognition region as a whole is implicated, rather than any one variant acting alone.
Positions joined since this page was written
What this is The text above discusses the variants this page was written around. Since then the catalogue has joined 3 more positions to it, by shared trait or shared paper. They are listed here by the paper each came from; the text does not describe them, and each variant page carries that study's own record.
Sakaue S et al. 2021, Nature genetics rs56036302 (TSBP1-AS1), rs2523571 (HLA-B) — PMID:34594039
Li Y et al. 2013, Nature genetics rs4282438 (COL11A2) — PMID:24097066
2025-09-24 · Genetic relationship between Sjögren's syndrome and abdominal aortic aneurysm: insights from a European population's genome-wide association analysis. Frontiers in Cardiovascular Medicine. 2025. DOI:10.3389/fcvm.2025.1554991
Sjögren's syndrome (SS, an autoimmune disease attacking moisture-producing glands) and abdominal aortic aneurysm (AAA) frequently coexist clinically, and this study investigated whether that reflects shared genetics rather than coincidence. Using European GWAS data (585 SS cases, 4,083 AAA cases), it found a significant positive genetic correlation (rg=0.32), 8 shared risk SNPs and 6 pleiotropic genes -- including HLA-B, HLA-DQB2 and LSM2 -- concentrated in the 6p22.2-21.32 region. Pathway analysis found strong enrichment for MHC class II antigen presentation and spliceosome/U6 snRNA binding, and tissue-specific analysis found shared heritability enrichment in artery/aorta, kidney and secretory tissues -- a genuinely coherent immune-vascular story rather than a statistical fluke. Immune cell co-localization implicated myeloid dendritic cells expressing HLA-DR (via rs9272318) in a shared dysregulation process. HLA-B itself was prioritized as a druggable target. The study's clinical suggestion: given this shared genetic and immunological basis, earlier AAA screening in Sjögren's patients may be clinically warranted, and HLA-pathway immunotherapies could theoretically address both conditions. This site's abdominal aortic aneurysm page carries 8 variants and Sjögren's syndrome page carries 3; none of HLA-B, HLA-DQB2 or LSM2 are currently on either.
Sjögren's syndrome is diagnosed by a combination of symptoms, eye and mouth tests, blood antibodies and sometimes a lip biopsy — not by genotype. None of the 3 variants on this page are used by any guideline to diagnose the condition.
The HLA region's association with Sjögren's syndrome is among the strongest ever measured for any variant on this site — but strength of statistical association is not the same as usefulness for prediction in one person. These are population-level findings from thousands of people, not an individual diagnostic test.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Sjögren's Syndrome comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 3 of 6 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
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Sjögren's Syndrome. MyGeneLog™. https://www.mygenelog.com/conditions/sjogrens-syndrome
Sjögren's syndrome is an autoimmune disease, affecting an estimated 0.7% of European Americans, in which the immune system attacks the glands that produce tears and saliva — typically causing dry eyes and dry mouth.
The HLA class II region, tagged here by rs115575857, reached a meta-analysis p-value of 7.65×10⁻¹¹⁴ in a 2013 study of 4,337 cases and 12,459 controls — one of the strongest genetic associations measured for any condition on this site.
The 2013 study confirmed 7 genome-wide-significant regions in total (HLA, IRF5-TNPO3, STAT4, IL12A, FAM167A-BLK, DDX6-CXCR5 and TNIP1); this page holds variants from 3 of them.
No. Sjögren's syndrome is diagnosed through symptoms, eye and mouth tests, blood antibodies and sometimes a lip biopsy — not genotype. These are population-level findings, not an individual diagnostic test.
Free to reuse. This page's text is original writing from freely-available research, licensed CC BY 4.0 — reuse it, including commercially, with attribution to MyGeneLog™. It's general research-derived information, not medical advice or a diagnosis — see Terms of Use.