Expressive

rs117026326 (GTF2I): Sjögren's Syndrome Risk Variant

Key takeaways

  • rs117026326 is one of the strongest known genetic risk signals for primary Sjögren's syndrome, an autoimmune disease targeting moisture-producing glands
  • The risk allele approximately doubles the odds of developing PSS, with a combined odds ratio of 2.20 in Han Chinese populations
  • The variant lies within the GTF2I gene at chromosomal region 7q11.23, with the signal extending into the neighboring GTF2IRD1 gene
  • The discovery was replicated across multiple independent cohorts, and a separate female-specific GWAS confirmed GWAS-level significance
  • No pharmacogenomic or lifestyle findings for this variant are documented in the available evidence

Key takeaways

  • rs117026326 is one of the strongest known genetic risk signals for primary Sjögren's syndrome (PSS), an autoimmune disease that targets moisture-producing glands
  • The risk allele approximately doubles the odds of developing PSS, with a combined odds ratio of 2.20 in Han Chinese populations
  • The variant lies within the GTF2I gene (General Transcription Factor IIi) at chromosomal region 7q11.23, with the association signal extending into the neighboring GTF2IRD1 gene
  • The discovery was replicated across multiple independent cohorts, and a separate female-specific GWAS confirmed GWAS-level significance
  • No pharmacogenomic or lifestyle findings for this variant are documented in the available evidence

What the research says A three-stage genome-wide association study (GWAS - a method scanning hundreds of thousands of genetic positions simultaneously to find disease-linked variants) in Han Chinese identified rs117026326 within GTF2I (General Transcription Factor IIi) at chromosomal region 7q11.23 as the leading susceptibility locus for PSS, reaching a combined p-value of 1.31 × 10^-5³ and a combined odds ratio of 2.20 across 1,845 total cases and 3,777 total controls spanning discovery and two independent replication stages; fine-mapping confirmed this variant as the peak signal, with associated variants spanning from GTF2I into the adjacent GTF2IRD1 gene PMID 25108384. A subsequent GWAS restricted to female Han Chinese patients - 242 cases and 1,444 controls in discovery, independently replicated in 178 cases and 14,432 controls - confirmed GWAS-level significance for the same variant, and proposed that while GTF2I may contribute to PSS through immune-system mechanisms, a co-identified gene (RBMS3) may separately predispose women through acinar cell apoptosis and TGF-β signaling in exocrine (moisture-producing gland) tissue PMID 28470504.

Reported associations

  • Primary Sjögren's syndrome, Han Chinese population (three-stage GWAS): rs117026326 in GTF2I at 7q11.23 was the top susceptibility hit; combined OR = 2.20; p = 1.31 × 10^-5³; 1,845 cases and 3,777 controls in total PMID 25108384
  • Female primary Sjögren's syndrome, Han Chinese population (female-specific GWAS): The same variant confirmed at GWAS significance in a female-only analysis; 242 discovery cases and 1,444 controls; independently replicated in 178 cases and 14,432 controls PMID 28470504

Evidence quality The association between rs117026326 and PSS is supported by strong statistical evidence: a combined p-value of 1.31 × 10^-5³ far exceeds the genome-wide significance threshold, and replication was built into the original three-stage study design using two independent cohorts PMID 25108384. A separate independent study in female patients later confirmed the signal in a wholly different sample PMID 28470504. No conflicting findings are reported between the two studies. Both were conducted exclusively in Han Chinese populations, so whether the association generalizes to non-East-Asian ancestries is not established by the available evidence.

Lifestyle considerations No lifestyle considerations on file for this variant.

Lifestyle context

Concrete actions anchored to the cited research. We do not prescribe, we describe.

Discuss with your doctor

  • Elevated genetic risk for SLE and Sjogren syndrome High

    rs117026326 T-allele substantially increases genetic risk for systemic lupus erythematosus (OR 1.9-2.1) and primary Sjogren syndrome (OR 2.2) with highly significant evidence

    Discuss baseline anti-nuclear antibody testing and key symptoms (joint pain, dry eyes, dry mouth) with your doctor

Frequently asked questions

What is the GTF2I gene?

GTF2I, also called General Transcription Factor IIi, is a gene located at chromosomal region 7q11.23. Studies suggest it may play a role in the immune system, and it has been identified as the leading susceptibility gene for primary Sjögren's syndrome in Han Chinese populations.

Is rs117026326 linked to Sjögren's syndrome?

Yes. Two genome-wide association studies in Han Chinese populations found rs117026326 strongly associated with primary Sjögren's syndrome. The risk allele roughly doubles the odds (combined OR = 2.20), and the association reached one of the lowest p-values ever reported for an autoimmune trait.

What is primary Sjögren's syndrome?

Primary Sjögren's syndrome is an autoimmune disease in which the immune system attacks the body's moisture-producing glands, causing dryness and other symptoms. It affects women far more often than men and tends to have its peak onset around menopause.

Has rs117026326 been studied in non-Asian populations?

The studies available for this variant were conducted exclusively in Han Chinese populations. Whether the same strong association exists in non-East-Asian populations has not been established by the reviewed evidence.

What does the 7q11.23 chromosomal region mean?

7q11.23 is a specific address on chromosome 7, where the GTF2I gene and neighboring GTF2IRD1 gene are located. The rs117026326 variant sits in this region, and multiple nearby variants also showed association signals in the Sjögren's syndrome GWAS.