Expressive

rs117048639 (FN3KRP-FN3K): Blood Biomarker Locus

Key takeaways

  • rs117048639 lies within the FN3KRP-FN3K locus, identified in a 363,000-person UK Biobank study of 35 blood and urine measurements.
  • The broader analysis catalogued 1,857 genomic regions tied to at least one blood or urine biomarker, with 3,374 fine-mapped associations.
  • Tissue expression data link this variant to reduced activity of two genes in artery tissue: CENPX in coronary arteries and ENSG00000262410 in tibial arteries.
  • The study spanned multiple ancestry groups, supporting the cross-population relevance of its findings.

Key takeaways

  • rs117048639 lies within the FN3KRP-FN3K locus, identified in a 363,000-person UK Biobank study of 35 blood and urine measurements.
  • The broader analysis catalogued 1,857 genomic regions tied to at least one blood or urine biomarker, with 3,374 fine-mapped associations.
  • Tissue expression data link this variant to reduced activity of two genes in artery tissue: CENPX in coronary arteries and ENSG00000262410 in tibial arteries.
  • The study spanned multiple ancestry groups including African and South Asian populations, supporting the cross-population breadth of its findings.

What the research says A genome-wide association study (GWAS) of 35 blood and urine biomarkers in 363,228 UK Biobank participants, with meta-analysis extending to 355,891 individuals across White British, non-British White, African, and South Asian populations, identified 1,857 genomic loci significantly associated with at least one clinical laboratory measurement, among which the FN3KRP-FN3K locus was characterized. PMID 33462484 Fine-mapping of these regions yielded 3,374 distinct associations, and additional analyses characterized large-effect protein-altering variants, human leukocyte antigen (HLA) allele associations, and copy number variants (CNVs) across the 35 biomarkers. PMID 33462484 Mendelian Randomization analysis within the same study identified 51 causal relationships between biomarker levels and disease outcomes, situating this locus within a broader network of genetically influenced clinical measurements. PMID 33462484

Reported associations

  • Blood and urine biomarkers (35-panel): rs117048639 at this locus is among 1,857 genomic regions identified as significantly associated with at least one of 35 measured laboratory traits in the UK Biobank cohort (n=363,228); specific per-trait effect sizes for this locus are detailed in the full study results. PMID 33462484

Evidence quality The primary study enrolled 363,228 unrelated UK Biobank participants across 5 ancestry groups and applied a stringent Bonferroni-corrected significance threshold of p < 5x10^-9 for imputed and directly genotyped variants. PMID 33462484 LD Score regression intercepts across all 35 phenotypes ranged from 0.999 to 1.137, indicating well-controlled population stratification - meaning the associations are unlikely to be inflated by ancestry differences within the sample. PMID 33462484 Effect size estimates showed high agreement when compared against 42 previously published cohorts across 25 of the 35 biomarkers, supporting the reliability of the broader set of associations reported in the study. PMID 33462484 No conflicting findings for rs117048639 specifically are described in the provided study materials.

Tissue-specific expression effects

  • CENPX: This variant is associated with reduced expression of the CENPX gene (Centromere Protein X) in coronary artery tissue. GTEx Portal
  • ENSG00000262410: This variant is associated with reduced expression of the ENSG00000262410 gene in tibial artery tissue. 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

  • HbA1c levels Moderate

    FN3K variant associated with elevated glycated hemoglobin in GWAS of 338919 individuals

    Annual HbA1c screening

Frequently asked questions

What is rs117048639?

rs117048639 is a genetic variant at the FN3KRP-FN3K locus, identified in a large UK Biobank genome-wide study of 35 blood and urine laboratory measurements across more than 363,000 participants.

What blood tests are linked to the FN3KRP-FN3K locus?

The study examined 35 blood and urine biomarkers and identified this locus as significantly associated with at least one of those measurements. The specific primary biomarker is detailed in the full study results and supplementary tables.

What does the arterial tissue expression data mean for rs117048639?

GTEx data show this variant is associated with lower activity of CENPX in coronary artery tissue and ENSG00000262410 in tibial artery tissue. These are potential biological mechanisms, but they do not confirm a disease association on their own.

How many people were in the study that identified rs117048639?

The primary analysis used 363,228 UK Biobank participants, with meta-analysis extending to 355,891 individuals across White British, non-British White, African, and South Asian ancestry groups.

Was the rs117048639 finding validated in other studies?

The UK Biobank study compared its effect sizes to 42 other published cohorts across 25 of the 35 biomarkers and found high agreement overall. Independent replication specifically for rs117048639 is not described in the provided study materials.