Expressive

rs10487851 (NRCAM): COPD protein marker and lung eQTL

Key takeaways

  • rs10487851 is a variant near NRCAM identified in a study of blood protein markers in approximately 1,340 current and former smokers.
  • The ALT allele increases NRCAM expression in lung, colon, and immune cells according to GTEx data from 953 donors.
  • This variant was found in a pQTL study, which links genetic variants to protein levels in blood - a distinct layer from gene expression alone.
  • The specific blood protein this variant influences is not named in the available source text.
  • The source study used a strict significance threshold and required replication across two independent cohorts.

Key takeaways

  • rs10487851 is a variant near the NRCAM (neuronal cell adhesion molecule) gene identified in a study of blood protein markers in approximately 1,340 current and former smokers.
  • The ALT allele increases NRCAM expression in lung, colon, and immune cells according to GTEx reference data from 953 donors.
  • This variant was found in a pQTL study, which links genetic variants to protein levels in blood - a distinct layer from gene expression (mRNA) alone.
  • The specific blood protein this variant influences is not named in the available source text.
  • The source study used a strict significance threshold and required replication across two independent cohorts, which is a methodological strength.

What the research says A meta-analysis examining protein quantitative trait loci (pQTLs) - genetic variants associated with measured blood protein levels - in two large cohorts of current and former smokers (SPIROMICS, N=750; COPDGene, N=590) identified 527 highly significant pQTLs (p < 8x10^-10) across 38 of 88 blood proteins tested, with most pQTL variants showing low overlap with expression QTLs, suggesting distinct biological mechanisms PMID 28594818. The study found that some variants explained more than 10% of measured protein variation and that incorporating pQTL genotypes into predictive models improved explanation of COPD-related phenotypes such as emphysema PMID 28594818. GTEx reference data show that the ALT allele at rs10487851 is associated with increased NRCAM expression in lung, colon transverse, and EBV-transformed lymphocytes GTEx Portal.

Reported associations

  • Blood protein biomarker variation (COPD context): This variant appears in a pQTL analysis of 88 blood proteins in approximately 1,340 current and former smokers, within a study that identified 527 highly significant pQTL variants; the specific protein linked to rs10487851 is not named in the provided source text PMID 28594818.
  • NRCAM tissue expression: The ALT allele is associated with increased NRCAM expression across three tissues - lung, colon transverse, and EBV-transformed lymphocytes (a laboratory immune cell model) - with effect slopes consistently in the positive direction GTEx Portal.

Evidence quality The pQTL source study enrolled approximately 1,340 participants across two well-characterized cohorts (SPIROMICS N=750; COPDGene N=590), all of whom were current or former smokers, and applied a conservative significance threshold (p < 8x10^-10) with cross-cohort replication PMID 28594818. However, the provided text does not specify which blood protein this variant was found to influence, nor its effect size for that protein, and no independent replication study targeting rs10487851 specifically is available from the provided sources. The GTEx eQTL data derive from 953 donors across multiple tissues at FDR < 0.05, providing a well-powered tissue expression reference GTEx Portal. The exclusive enrollment of smokers limits generalizability to the general population, and evidence for this variant should be considered preliminary.

Tissue-specific expression effects

  • NRCAM: The ALT allele is associated with increased expression in colon transverse (strongest signal, p=1.6e-9), EBV-transformed lymphocytes (p=9.2e-5), and lung (p=9.7e-5); all three tissues show increased expression with the ALT allele GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is the NRCAM gene?

NRCAM stands for neuronal cell adhesion molecule. It encodes a protein involved in cell-to-cell adhesion and signaling, with roles in the nervous system as well as other tissues including lung and immune cells.

What is a pQTL and how is it different from an eQTL?

A pQTL (protein quantitative trait locus) is a genetic variant associated with the measured level of a protein in blood or tissue. Unlike an eQTL, which affects gene activity at the mRNA level, a pQTL can influence protein abundance through post-transcriptional mechanisms, meaning the two types of variants often do not overlap.

Is rs10487851 linked to COPD?

rs10487851 was identified in a study examining protein biomarkers in people with and without COPD, but the available evidence does not establish a direct causal link between this specific variant and COPD disease risk. The study focused on protein level variation, not disease susceptibility.

Which tissues show expression changes linked to rs10487851?

GTEx reference data show that the ALT allele at rs10487851 is associated with increased NRCAM gene expression in three tissues: colon transverse, EBV-transformed lymphocytes, and lung. The colon transverse association had the strongest statistical signal of the three.