Expressive

rs117875848 (OR4X2/OR4X1): Biomarker GWAS Variant

Key takeaways

  • This variant sits near olfactory receptor genes OR4X2 and OR4X1 but shows expression effects in blood, nerve, lung, brain, and muscle - not smell-related tissue.
  • Its strongest signal is increased MYBPC3 (a cardiac muscle protein gene) expression in whole blood (p=1.2e-12).
  • FOLH1 expression increases in brain cortex and skin; PTPRJ expression decreases in the brain putamen while C1QTNF4 increases in the nucleus accumbens.
  • This variant was identified in a UK Biobank GWAS of 35 blood and urine biomarkers across more than 363,000 participants.
  • The specific biomarker this variant is associated with is not detailed in the available evidence.

Key takeaways

  • This variant sits near olfactory receptor genes OR4X2 and OR4X1 but shows expression effects in blood, nerve, lung, brain, and muscle - not smell-related tissue.
  • Its strongest signal is increased MYBPC3 (a cardiac muscle protein gene) expression in whole blood (p=1.2e-12).
  • FOLH1 expression increases in brain cortex and skin; PTPRJ expression decreases in the brain putamen while C1QTNF4 increases in the nucleus accumbens.
  • This variant was identified in a UK Biobank GWAS of 35 blood and urine biomarkers across more than 363,000 participants.
  • The specific biomarker this variant is associated with is not detailed in the available evidence.

What the research says rs117875848 is located at the OR4X2 - OR4X1 locus, named for two olfactory receptor genes (proteins that detect smells), though its regulatory effects extend well beyond smell-related biology. The associated UK Biobank study applied a genome-wide association design (GWAS, scanning millions of genetic variants simultaneously for statistical links to measured traits) across 35 clinical blood and urine biomarkers in 363,228 individuals from five ancestry groups, with fine-mapping identifying 3,374 credible associations across 1,857 loci genome-wide. GTEx v11 data (953 donors, FDR<0.05), which measures how genetic variants relate to gene activity levels across tissues, identifies this variant as influencing expression of five genes - MYBPC3, FOLH1, PTPRJ, FNBP4, and C1QTNF4 - across blood, brain, nerve, lung, muscle, and skin GTEx Portal.

Reported associations

  • Blood and urine biomarkers (UK Biobank GWAS): This variant was identified in a systematic GWAS of 35 clinical measurements including lipids, glycemic traits, and kidney and liver function markers in 363,228 participants across five ancestry groups. The specific biomarker(s) associated with this variant are not described in the available study text.
  • MYBPC3 expression (myosin-binding protein C, cardiac type - a structural protein in heart muscle): The alternate allele is associated with increased expression in whole blood (slope +0.36, p=1.2e-12), tibial nerve (slope +0.53, p=3.8e-4), and lung (slope +0.42, p=5.8e-5) GTEx Portal.
  • FOLH1 expression (folate hydrolase 1, also called PSMA): The alternate allele is associated with increased expression in sun-exposed lower leg skin (slope +0.39, p=3.9e-4) and brain cortex (slope +0.37, p=7.1e-8) GTEx Portal.
  • PTPRJ expression (protein tyrosine phosphatase receptor type J, a cell signaling molecule): The alternate allele is associated with reduced expression in the brain putamen (a basal ganglia region involved in movement and habit learning; slope -0.54, p=2.1e-4) GTEx Portal.
  • FNBP4 expression (formin-binding protein 4, involved in cytoskeleton organization): The alternate allele is associated with reduced expression in skeletal muscle (slope -0.29, p=1.1e-5) GTEx Portal.
  • C1QTNF4 expression (complement C1q tumor necrosis factor-related protein 4, a secreted signaling protein): The alternate allele is associated with increased expression in the nucleus accumbens (a basal ganglia region linked to reward processing; slope +0.33, p=1.6e-4) GTEx Portal.

Evidence quality The UK Biobank GWAS applied stringent Bonferroni-corrected significance thresholds (p < 5 x 10^-9 for imputed variants), fine-mapped 3,374 associations across 1,857 loci, and spanned five ancestry groups (White British n=318,953; non-British White n=23,582; African n=6,019; South Asian n=7,338; East Asian n=1,082). The GTEx eQTL results come from v11 (953 donors) at FDR<0.05. The MYBPC3 whole blood eQTL (p=1.2e-12) is one of the stronger signals in the dataset; the brain and muscle eQTL signals, while passing significance thresholds, rest on smaller within-tissue sample sizes and should be treated as preliminary. The specific biomarker phenotype(s) this variant is associated with in the GWAS are not described in the provided study text, so phenotypic consequences of this locus cannot be fully characterized from the available evidence. No independent replication of the eQTL signals is described in the provided data.

Tissue-specific expression effects

  • MYBPC3: Increased expression in whole blood, tibial nerve, and lung in carriers of the alternate allele GTEx Portal.
  • FOLH1: Increased expression in sun-exposed lower leg skin and brain cortex GTEx Portal.
  • PTPRJ: Reduced expression in brain putamen (a basal ganglia region involved in movement and learning) GTEx Portal.
  • FNBP4: Reduced expression in skeletal muscle GTEx Portal.
  • C1QTNF4: Increased expression in the nucleus accumbens (a basal ganglia region involved in reward and motivation) GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What genes are near rs117875848?

rs117875848 is located near OR4X2 and OR4X1, both olfactory receptor genes involved in detecting smells. Despite this location, GTEx eQTL data shows the variant influences expression of other genes including MYBPC3, FOLH1, PTPRJ, FNBP4, and C1QTNF4 across multiple tissues unrelated to smell.

What is MYBPC3 and why does this variant affect it?

MYBPC3 (myosin-binding protein C, cardiac type) is a structural protein important in heart muscle function. GTEx data shows this variant is associated with increased MYBPC3 expression in whole blood, tibial nerve, and lung, with a very strong statistical signal in blood (p=1.2e-12). The clinical relevance of this eQTL effect has not been established in the available evidence.

Is rs117875848 linked to any blood tests or health conditions?

This variant was identified in a UK Biobank genome-wide association study of 35 clinical blood and urine measurements, including lipids, glycemic markers, and kidney and liver function tests in 363,228 participants. The specific measurement(s) it is associated with are not described in the currently available study data.

Does rs117875848 affect brain gene expression?

Yes. GTEx data shows this variant is associated with increased FOLH1 expression in brain cortex, increased C1QTNF4 expression in the nucleus accumbens, and reduced PTPRJ expression in the putamen. Whether these changes influence brain function or behavior is not established by current evidence.

What is an eQTL and why does it matter for this variant?

An eQTL (expression quantitative trait locus) is a genetic variant that influences how much a nearby gene is produced in a specific tissue. GTEx data identifies rs117875848 as an eQTL for five genes across blood, brain, skin, lung, and muscle, suggesting it has broad regulatory effects rather than a single focused function.