Expressive

rs10784885 (TSPAN8): Gut Microbiota & Liver eQTL

Key takeaways

  • This variant sits between the PTPRR and TSPAN8 genes and has been studied in relation to gut microbiota composition in a Japanese cohort
  • Tissue-level expression data show the alternate allele substantially reduces TSPAN8 activity in the liver, with a strong statistical signal (p = 3.6 × 10^-¹^0)
  • The gut microbiota evidence comes from a single GWAS of 1,068 Japanese adults and has not been independently replicated in the supplied materials
  • Gut microbiota genetics appear highly polygenic - identified variants each explain only a small fraction of microbiome variation

Key takeaways

  • This variant sits between the PTPRR and TSPAN8 genes and has been studied in relation to gut microbiota composition in a Japanese cohort
  • Tissue-level expression data show the alternate allele substantially reduces TSPAN8 activity in the liver, with a strong statistical signal (p = 3.6 × 10^-¹^0)
  • The gut microbiota evidence comes from a single GWAS of 1,068 Japanese adults and has not been independently replicated in the supplied materials
  • Gut microbiota genetics appear highly polygenic - identified variants each explain only a small fraction of microbiome variation

What the research says A genome-wide association study (GWAS) of 1,068 healthy Japanese adults (Ishida et al., Communications Biology, 2021) examined gut microbiota composition after controlling for 138 extrinsic and demographic covariates including diet, medication, and physical activity; the authors concluded that microbiota composition is governed by a highly polygenic architecture, with any single locus accounting for only a small fraction of microbiota variability. Tissue-level expression data from GTEx v11 (953 donors) show that the alternate allele at this locus is linked to reduced TSPAN8 (Tetraspanin 8) expression in liver and tibial artery tissue, increased PTPRB expression in visceral omental adipose tissue, and increased expression of the neighboring annotated locus ENSG00000258053 in tibial nerve tissue GTEx Portal.

Reported associations

  • Gut microbiota composition: this locus was examined in a GWAS of 1,068 healthy Japanese adults; associated variants collectively explained only a small fraction of microbiota variability (Ishida et al., Communications Biology, 2021)
  • TSPAN8 liver expression: the alternate allele is linked to reduced TSPAN8 expression in liver tissue (eQTL slope −0.42 per allele, p = 3.6 × 10^-¹^0) GTEx Portal
  • TSPAN8 tibial artery expression: the alternate allele is linked to reduced TSPAN8 expression in tibial artery tissue (eQTL slope −0.09 per allele, p = 1.2 × 10^-5) GTEx Portal
  • PTPRB visceral adipose expression: the alternate allele is linked to increased PTPRB (Protein Tyrosine Phosphatase Receptor Type B) expression in visceral omental adipose tissue (eQTL slope +0.09 per allele, p = 3.0 × 10^-6); PTPRB is a distinct gene from the PTPRR named in the variant label GTEx Portal
  • ENSG00000258053 tibial nerve expression: the alternate allele is linked to increased expression of a neighboring annotated genomic locus in tibial nerve tissue (eQTL slope +0.11 per allele, p = 2.1 × 10^-5) GTEx Portal

Evidence quality The human phenotype evidence derives from a single GWAS of 1,068 Japanese adults (Ishida et al., Communications Biology, 2021) that incorporated 138 demographic and lifestyle covariates to isolate genetic signals; the study has no PMID in the supplied metadata, so direct citation links are unavailable. The authors identified five genome-wide significant loci in total and explicitly stated that these collectively explain only a small fraction of gut microbiota variability, underscoring the polygenic nature of the trait. No independent replication cohort data are provided in the supplied materials, limiting confidence in interpreting any single locus in isolation. The GTEx eQTL data, drawn from 953 donors across multiple tissues and filtered at FDR < 0.05, represent the most statistically robust signals documented for this locus; the liver TSPAN8 association is particularly strong (p = 3.6 × 10^-¹^0).

Tissue-specific expression effects

  • TSPAN8: the alternate allele is associated with reduced expression in liver (slope −0.42, p = 3.6 × 10^-¹^0) and in tibial artery (slope −0.09, p = 1.2 × 10^-5); these are tissue-level mechanistic signals, not clinical outcome measures GTEx Portal
  • PTPRB: the alternate allele is associated with increased expression in visceral omental adipose tissue (slope +0.09, p = 3.0 × 10^-6); this is a distinct gene from PTPRR despite the similar name GTEx Portal
  • ENSG00000258053: the alternate allele is associated with increased expression in tibial nerve tissue (slope +0.11, p = 2.1 × 10^-5) GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What genes are near rs10784885?

rs10784885 sits in the intergenic region between PTPRR (Protein Tyrosine Phosphatase Receptor Type R) and TSPAN8 (Tetraspanin 8). Expression data also show effects on the nearby gene PTPRB, which is related to but distinct from PTPRR.

Is rs10784885 linked to gut microbiota?

A genome-wide association study of 1,068 healthy Japanese adults found this locus to be among the variants associated with gut microbiota diversity measures. The study's authors noted that identified loci each explain only a small fraction of overall microbiome variability, pointing to a highly polygenic trait.

What does rs10784885 do to TSPAN8 expression in the liver?

GTEx expression data from 953 donors show that the alternate allele at rs10784885 is associated with reduced TSPAN8 expression in liver tissue, with a per-allele slope of −0.42 (log2-normalized) and a p-value of 3.6 × 10^-¹^0. This is a mechanistic, tissue-level signal rather than a clinical outcome measure.

Which tissues are affected by rs10784885?

GTEx data indicate effects in at least four tissue types: liver and tibial artery (both showing reduced TSPAN8 expression), visceral omental adipose tissue (increased PTPRB expression), and tibial nerve tissue (increased expression of the neighboring annotated locus ENSG00000258053).

How reliable is the evidence for rs10784885?

The gut microbiota association comes from a single study with no independent replication supplied. The tissue expression findings from GTEx are based on 953 donors and pass a strict false-discovery-rate threshold, making them the most statistically robust signals in the available evidence.