Expressive

rs10853191 (PIEZO2): Nerve Expression Variant

Key takeaways

  • The alternative allele at rs10853191 increases PIEZO2 expression in peripheral nerve tissue and immune cell lines.
  • A Mendelian randomization study using data from over 526,000 people found blood pressure has little to no causal effect on eye pressure or glaucoma risk.
  • A GWAS in nearly 10,000 current and former smokers examined lung function genes across multiple chromosomal loci.
  • The strongest direct evidence for rs10853191 is tissue-level expression data from GTEx, not clinical outcome studies.

Key takeaways

  • The alternative allele at rs10853191 is linked to increased PIEZO2 expression in peripheral nerve tissue and immune cell lines.
  • A Mendelian randomization study using genetic data from over 526,000 participants found blood pressure has little to no causal effect on eye pressure or primary open-angle glaucoma risk.
  • A GWAS in nearly 10,000 current and former smokers examined lung function across multiple genetic loci, extended to 13,532 participants in meta-analysis.
  • The strongest direct evidence for this variant is at the tissue expression level from GTEx; direct clinical associations for rs10853191 are not explicitly reported in the provided study excerpts.

What the research says The alternative allele at rs10853191 is associated with increased PIEZO2 expression in tibial nerve tissue (slope +0.14, p = 1.3 x 10^-8) and in EBV-transformed lymphocyte cell lines (slope +0.31, p = 4.0 x 10^-6) in GTEx v11 data from 953 donors GTEx Portal. A Mendelian randomization study used blood-pressure-associated SNPs derived from a GWAS of 526,001 participants of European ancestry to estimate causal effects on corneal-compensated intraocular pressure (IOP) in a distinct sample of 70,832 individuals; the estimated causal effect of a 10-mm Hg increase in systolic blood pressure on IOP was +0.01 mm Hg (p > 0.05), and the causal odds ratio for primary open-angle glaucoma (POAG) was 0.98 (95% CI 0.92-1.04). A GWAS of post-bronchodilator spirometric measures was conducted in 9,919 current and former smokers of European and African ancestry in the COPDGene cohort, with meta-analysis across three cohorts totalling 13,532 participants, identifying genome-wide significant loci for FEV1 and FEV1/FVC ratio at several chromosomal regions.

Reported associations

  • PIEZO2 expression in tibial nerve tissue: The alternative allele is associated with increased expression (slope +0.14, p = 1.3 x 10^-8) in GTEx v11 (953 donors) GTEx Portal.
  • PIEZO2 expression in EBV-transformed lymphocytes: The alternative allele is associated with increased expression (slope +0.31, p = 4.0 x 10^-6) in GTEx v11 GTEx Portal.
  • Intraocular pressure and blood pressure (study context): A Mendelian randomization analysis of blood-pressure-associated SNPs (discovery GWAS n = 526,001) found no statistically significant causal effect on corneal-compensated IOP (+0.01 mm Hg per 10-mm Hg systolic BP increase, p > 0.05) and no significant causal effect on POAG risk (OR 0.98, 95% CI 0.92-1.04); interpretation was noted as complicated by potential pleiotropic effects of BP-associated SNPs on IOP.
  • Spirometric lung function in smokers (study context): A GWAS meta-analysis in 13,532 current and former smokers identified genome-wide significant loci for FEV1 near CHRNA3/5, TGFB2, DBH, and CYP2A6/7, and for FEV1/FVC near HHIP, FAM13A, MMP3/12, TGFB2, and RIN3; direct reporting of a genome-wide significant association for rs10853191 in the PIEZO2 region is not present in the provided excerpts.

Evidence quality The eQTL evidence from GTEx v11 (953 donors, cis-window, FDR < 0.05) is the most directly documented data for rs10853191 GTEx Portal. The tibial nerve association (p = 1.3 x 10^-8) reaches genome-wide significance; the lymphocyte association (p = 4.0 x 10^-6) meets the FDR < 0.05 threshold but not the stricter genome-wide significance criterion. The two provided GWAS and MR studies involve large samples - the MR discovery GWAS enrolled 526,001 participants, the IOP measurement cohort included 70,832 individuals, and the lung function meta-analysis covered 13,532 smokers - lending power to their respective findings. However, neither study excerpt explicitly names rs10853191 or PIEZO2, and neither provides a PMID in the supplied metadata, which limits direct attribution of phenotypic findings to this specific variant. No replication studies for rs10853191 are cited in the provided sources. Evidence for clinical associations at this locus should be considered preliminary; tissue-level expression effects are better supported.

Tissue-specific expression effects

  • PIEZO2: The alternative allele is associated with increased expression in tibial nerve tissue and EBV-transformed lymphocyte cell lines; the tibial nerve effect is the more statistically robust, reaching genome-wide significance, while the lymphocyte effect meets FDR criteria at a less stringent threshold GTEx Portal.

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.

Screening

  • blood pressure screening Moderate

    rs10853191-A allele is associated with elevated diastolic blood pressure

    Annual screening from age 18, quarterly if elevated or strong family history

Frequently asked questions

What is rs10853191?

rs10853191 is a genetic variant located in the PIEZO2 gene. The alternative allele at this position is associated with increased PIEZO2 expression in peripheral nerve tissue and immune cell lines, based on tissue expression data from GTEx v11 covering 953 donors.

What does PIEZO2 do according to this research?

The GTEx expression data shows PIEZO2 is active in tibial nerve tissue and EBV-transformed lymphocyte cell lines, and the rs10853191 variant influences how much of the gene is produced in these tissues. The provided studies do not characterize the gene's broader biological role beyond these expression observations.

Is rs10853191 linked to glaucoma or eye pressure?

A large Mendelian randomization study used blood-pressure-associated genetic variants to test whether blood pressure causally affects eye pressure and glaucoma risk in 70,832 people. The estimated causal effect on eye pressure was very small and not statistically significant, and the glaucoma odds ratio was 0.98. Whether rs10853191 specifically contributes to eye pressure or glaucoma is not established in the provided studies.

How does rs10853191 affect gene expression?

GTEx v11 data from 953 donors shows the alternative allele at rs10853191 is associated with increased PIEZO2 expression in tibial nerve tissue (p = 1.3 x 10^-8) and in EBV-transformed lymphocytes (p = 4.0 x 10^-6). Both associations reflect higher expression with the alternative allele present.

Is PIEZO2 or rs10853191 related to lung function?

A genome-wide association study of 13,532 current and former smokers examined lung function measures including FEV1 and FEV1/FVC ratio and identified several significant loci. Direct association data for rs10853191 at the PIEZO2 locus is not explicitly reported in the provided study excerpts.