Expressive

rs10823500 (PPA1 - NPFFR1): Plasma Protein QTL

Key takeaways

  • rs10823500 is associated with higher circulating PPA1 protein levels in blood, found in genome-wide studies of up to 10,708 participants.
  • The same variant increases PPA1 gene expression in skeletal muscle, tibial artery, aorta, heart, and digestive tissues.
  • The skeletal muscle eQTL signal is exceptionally strong (p=2.6x10-127) based on GTEx data from 953 tissue donors.
  • No clinical disease outcomes or lifestyle factors are directly linked to this variant in the available research.

Key takeaways

  • rs10823500 is associated with circulating PPA1 protein levels in blood, identified as a protein-quantitative trait locus (pQTL) in genome-wide proteomics studies covering thousands of participants.
  • The alternate allele of this variant is linked to increased PPA1 gene expression across eight body tissues, including skeletal muscle, arteries, and the heart.
  • Evidence combines two large independent plasma proteomics studies (up to 10,708 participants) with tissue expression data from 953 donors.
  • No clinical disease outcomes or lifestyle factors have been directly studied for this specific variant in the available research.

What the research says Two independent genome-wide association studies of circulating plasma protein levels identified rs10823500 as a variant associated with PPA1 protein concentrations in blood. The larger study profiled 4,775 proteins in 10,708 Fenland participants, identifying 10,674 variant-protein associations and constructing a proteo-genomic disease map covering 1,859 gene-protein-phenotype triplets. A separate KORA cohort study (n=1,000 discovery; n=338 replication in the QMDiab Arab and Asian cohort) identified 539 pQTLs at a Bonferroni-corrected threshold, with 82.2% of well-powered associations confirmed in the independent replication sample. GTEx v11 eQTL data from 953 donors (FDR<0.05) corroborates the association at the gene-expression level, showing the alternate allele is linked to increased PPA1 expression across multiple tissues GTEx Portal.

Reported associations

  • PPA1 plasma protein levels (pQTL - Fenland cohort): rs10823500 is associated with circulating PPA1 protein concentrations in 10,708 participants; the study applied a genome-proteome-wide significance threshold (p<1.004x10-11) across 4,775 proteins, and 64% of novel pQTLs replicated in an independent validation set.
  • PPA1 plasma protein levels (pQTL - KORA cohort): A second study (n=1,000 primary; n=338 QMDiab replication) identified pQTLs at p<8.72x10-11; 50.6% of associations met a Bonferroni replication threshold and 83.1% reached at least nominal significance in the replication cohort, with directional consistency confirmed for most replicated signals.
  • PPA1 gene expression (eQTL - multiple tissues): The alternate allele of rs10823500 is associated with increased PPA1 expression in skeletal muscle (p=2.6x10-127), tibial artery (p=1.3x10-95), esophagus muscularis (p=1.9x10-56), esophagus at the gastroesophageal junction (p=1.3x10-44), aorta (p=1.1x10-44), sigmoid colon (p=2.0x10-43), heart atrial appendage (p=1.0x10-36), and stomach (p=2.4x10-32) GTEx Portal.

Evidence quality The pQTL evidence rests on two large genome-wide plasma proteomics studies with stringent significance thresholds. The Fenland study (n=10,708) applied a genome-proteome-wide threshold (p<1.004x10-11) and reported that replication was higher for cis variants (81.2%) than trans variants (44.2%), suggesting cis-pQTLs like those for PPA1 are more reliably confirmed. The KORA study (n=1,000) applied a conservative Bonferroni correction (p<8.72x10-11) and achieved 82.2% replication among well-powered associations in QMDiab (n=338), with 95.2% reaching nominal significance; directional consistency was confirmed for the majority of replicated SNPs. Both studies used the aptamer-based SOMAscan proteomics platform; the Fenland study notes that mass spectrometry is the gold standard but lacks throughput for population-scale work, positioning aptamer-based assays as practical alternatives with platform-specific caveats. The GTEx eQTL signals are exceptionally strong statistically (skeletal muscle p=2.6x10-127, FDR<0.05) from 953 donors, with all eight tissue signals in the same direction (increased expression) and no conflicting findings GTEx Portal. No conflicting findings are present across the provided studies. The clinical relevance of these pQTL and eQTL associations requires further functional and disease-outcome studies specific to this variant; current evidence is preliminary in that respect.

Tissue-specific expression effects

  • PPA1: The alternate allele is associated with increased expression across eight tissues. The strongest effects are in skeletal muscle and the tibial artery, with additional increases in the esophagus (both the muscularis and gastroesophageal junction regions), the aorta, the sigmoid colon, the heart atrial appendage, and the stomach. All reported tissue effects are in the same direction (increased expression) with no conflicting signals GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs10823500 associated with?

rs10823500 is associated with the level of PPA1 protein circulating in blood and with increased PPA1 gene expression in several tissues including skeletal muscle, arteries, and the heart. These associations come from large-scale genome-wide proteomics studies and tissue gene expression databases.

What genes are near rs10823500?

rs10823500 sits in a genomic region containing two genes: PPA1 and NPFFR1. The available research specifically links this variant to PPA1 protein levels in blood and PPA1 gene expression in multiple tissues.

Which tissues show changed PPA1 expression with rs10823500?

GTEx data from 953 donors shows the alternate allele is linked to increased PPA1 expression in skeletal muscle, the tibial artery, the aorta, two regions of the esophagus (muscularis and gastroesophageal junction), the sigmoid colon, the stomach, and the heart atrial appendage. All eight effects point in the same direction.

Is rs10823500 linked to any disease?

The studies provided identify rs10823500 as a plasma protein QTL and tissue expression QTL. While the broader proteomics studies that found this variant also mapped protein-disease connections across thousands of traits, no specific disease association for rs10823500 itself is reported in the available evidence.

How reliable is the evidence for rs10823500?

The pQTL evidence comes from two large independent studies (up to 10,708 participants) with stringent significance thresholds and cross-ethnic replication. GTEx eQTL signals reach p=2.6x10-127 in skeletal muscle across 953 donors. These are statistically robust findings, though clinical validation specific to this variant has not been reported in the available research.