Expressive

rs115674093 (HLA-DOA/HLA-DPA1): HLA Gene Expression

Key takeaways

  • This variant acts as an eQTL, influencing how much nearby HLA genes are expressed rather than altering the gene sequences themselves.
  • The alternate allele increases HLA-DRB5, HLA-DRB1, and HLA-DQB1-AS1 expression across multiple tissues.
  • The same allele decreases HLA-DQA2 expression in brain cortex (largest magnitude effect: slope -0.85) and tibial artery.
  • Effects are observed across brain, muscle, vascular, and breast tissue.
  • No replicated disease or trait associations for this variant appear in the available evidence.

Key takeaways

  • This variant sits in the HLA-DOA and HLA-DPA1 genomic region and functions as an expression quantitative trait locus (eQTL), meaning it influences how much nearby genes are produced rather than changing the gene sequences themselves.
  • The alternate allele simultaneously increases expression of HLA-DRB5, HLA-DRB1, and HLA-DQB1-AS1 while decreasing expression of HLA-DQA2 across the tissues tested.
  • HLA-DQA2 shows the largest magnitude effect in the data: a slope of -0.85 in brain cortex, indicating substantially reduced expression when the alternate allele is present.
  • Effects are observed across brain, muscle, vascular, and breast tissue.
  • Current evidence rests on eQTL data alone; no replicated disease or trait associations for this variant appear in the available sources.

What the research says A large-scale GWAS method called Quickdraws was applied to 405,088 UK Biobank participants across 79 quantitative and 50 binary traits, using a spike-and-slab prior on variant effects that identified 4.97% more quantitative trait and 3.25% more binary trait associations than the REGENIE method. GTEx v11 data (953 donors, cis-window, FDR<0.05) identifies rs115674093 as an eQTL for at least four nearby HLA genes, with the alternate allele increasing expression of HLA-DRB5, HLA-DRB1, and HLA-DQB1-AS1 across several tissues while decreasing expression of HLA-DQA2 in brain cortex and tibial artery GTEx Portal. The strongest statistical association is HLA-DRB5 in tibial artery (effect slope +0.53, p=2.6e-7), and the largest magnitude effect is decreased HLA-DQA2 in brain cortex (slope -0.85, p=4.9e-5) GTEx Portal.

Reported associations

  • HLA-DRB5 expression (breast mammary tissue): Increased expression linked to the alternate allele (effect slope +0.64, p=9.3e-7) GTEx Portal
  • HLA-DRB5 expression (skeletal muscle): Increased expression (effect slope +0.54, p=1.7e-6) GTEx Portal
  • HLA-DRB5 expression (tibial artery): Increased expression (effect slope +0.53, p=2.6e-7) GTEx Portal
  • HLA-DQA2 expression (brain cortex): Decreased expression (effect slope -0.85, p=4.9e-5) GTEx Portal
  • HLA-DQA2 expression (tibial artery): Decreased expression (effect slope -0.54, p=5.8e-6) GTEx Portal
  • HLA-DRB1 expression (brain cortex): Increased expression (effect slope +0.60, p=4.6e-5) GTEx Portal
  • HLA-DRB1 expression (nucleus accumbens, basal ganglia): Increased expression (effect slope +0.52, p=2.5e-5) GTEx Portal
  • HLA-DQB1-AS1 expression (spinal cord cervical): Increased expression (effect slope +0.62, p=6.3e-5) GTEx Portal

Evidence quality All current associations for rs115674093 derive from GTEx v11 eQTL data (953 donors, FDR<0.05), which captures tissue-specific changes in gene expression rather than disease or trait outcomes. The p-values across the eight reported associations range from 2.5e-5 to 2.6e-7, all meeting the FDR<0.05 threshold. The largest single-tissue magnitude effect is decreased HLA-DQA2 expression in brain cortex (slope -0.85, p=4.9e-5), while HLA-DRB5 in tibial artery shows the most statistically significant association (p=2.6e-7). No independent replication of these eQTL effects appears in the provided sources. The GWAS study referenced here (Quickdraws, n=405,088 UK Biobank participants) documents a methodological advance for identifying biobank-scale associations, but the available excerpt does not report specific findings for this variant. Any trait-level interpretation should be considered preliminary.

Tissue-specific expression effects

  • HLA-DRB5: Increased expression in breast mammary tissue, skeletal muscle, and tibial artery when the alternate allele is present GTEx Portal
  • HLA-DQA2: Reduced expression in brain cortex and tibial artery GTEx Portal
  • HLA-DRB1: Increased expression in brain cortex and nucleus accumbens basal ganglia GTEx Portal
  • HLA-DQB1-AS1: Increased expression in spinal cord cervical tissue GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs115674093?

rs115674093 is a genetic variant in the HLA-DOA and HLA-DPA1 genomic region. GTEx data shows it functions as an expression quantitative trait locus (eQTL), meaning it influences how much certain nearby HLA genes are produced in different body tissues.

What genes does rs115674093 affect?

GTEx data links this variant to expression changes in four genes: HLA-DRB5, HLA-DQA2, HLA-DRB1, and HLA-DQB1-AS1. The alternate allele increases expression of three of these genes while decreasing HLA-DQA2 across the tissues tested.

Is rs115674093 linked to any diseases?

The available evidence is limited to tissue-specific gene expression data from GTEx. No direct disease or trait associations for this variant are documented in the sources reviewed for this entry. Expression QTL findings describe molecular mechanisms, not confirmed disease connections.

Why does rs115674093 increase some genes while decreasing another?

The GTEx data shows the alternate allele increases expression of HLA-DRB5, HLA-DRB1, and HLA-DQB1-AS1 while decreasing HLA-DQA2. The available sources do not explain the specific mechanism behind these opposing effects; the pattern is observed in the data but not further characterized.

What is an eQTL and what does it mean for this variant?

An eQTL (expression quantitative trait locus) is a genetic variant associated with changes in how much a nearby gene is expressed - that is, how much RNA or protein it produces. For rs115674093, the GTEx data shows it influences expression of several HLA genes across multiple tissues. This is a molecular finding and does not directly indicate health outcomes.