Expressive

rs118002512 (HS3ST6-MSRB1): Biomarker Locus

Key takeaways

  • This variant in the HS3ST6-MSRB1 region was identified in a UK Biobank study of 35 blood and urine biomarkers across more than 363,000 individuals.
  • GTEx data link this locus to increased expression of IGFALS, the protein that transports IGF-1 in blood, in brain and nerve tissues.
  • Expression effects span five genes: MEIOB, IGFALS, EME2, HAGH, and TELO2, across thyroid, brain, esophagus, and skin tissues.
  • No specific lifestyle considerations are currently on file for this variant.

Key takeaways

  • This variant in the HS3ST6-MSRB1 (heparan sulfate-glucosamine 3-sulfotransferase 6 / methionine sulfoxide reductase B1) region was identified in a UK Biobank study of 35 blood and urine biomarkers across more than 363,000 individuals.
  • GTEx data link this locus to increased expression of IGFALS, the protein that transports insulin-like growth factor 1 (IGF-1) in blood, in brain cerebellum, cerebellar hemisphere, and tibial nerve.
  • Expression effects span five genes, including increased expression of MEIOB in thyroid and skin, and reduced expression of TELO2 in brain putamen.
  • No specific lifestyle considerations are currently on file for this variant.

What the research says A genome-wide association study of 35 blood and urine biomarkers in the UK Biobank (n=363,228 individuals) identified 1,857 associated loci containing 3,374 fine-mapped associations, and rs118002512 falls within one such locus. The analysis applied Bonferroni-corrected significance thresholds (p < 5 x 10-9 for assayed and imputed variants) and validated polygenic risk score models in the independent FinnGen cohort (n=135,500). GTEx v11 eQTL data (953 donors) show that the alternate allele at this position increases expression of IGFALS in brain and nerve tissue and reduces expression of TELO2 in brain putamen GTEx Portal.

Reported associations

  • Blood and urine biomarkers: rs118002512 was identified within this locus in a GWAS of 35 clinical laboratory measurements in UK Biobank (n=363,228); the specific biomarker driving the association signal is not described in the available study excerpts.

Evidence quality The UK Biobank biomarker study used a discovery sample of up to 363,228 individuals drawn from five population groups, with meta-analysis across four groups (n=355,891), applying Bonferroni-corrected thresholds (p < 5 x 10-9 for imputed variants). Polygenic risk models were replicated in FinnGen (n=135,500), where they improved genetic risk stratification for chronic kidney disease, type 2 diabetes, gout, and alcoholic cirrhosis. GTEx eQTL signals at this locus reach genome-wide significance in thyroid tissue (MEIOB, p=2.4 x 10-9) and esophageal mucosa (EME2, p=3.5 x 10-8), while brain and nerve eQTL p-values range from 1.0 x 10-6 to 7.4 x 10-6 GTEx Portal. The specific GWAS effect size and significance level for rs118002512 itself are not available in the provided study excerpts, limiting direct assessment of primary association strength.

Tissue-specific expression effects

  • MEIOB (meiosis-specific OB-domain protein, involved in DNA repair during cell division): increased expression in thyroid gland and non-sun-exposed suprapubic skin GTEx Portal
  • IGFALS (insulin-like growth factor acid-labile subunit, which forms a ternary complex in blood that transports and extends the half-life of IGF-1): increased expression in brain cerebellum, brain cerebellar hemisphere, and tibial nerve GTEx Portal
  • EME2 (essential meiotic structure-specific endonuclease 2, a DNA damage repair enzyme): increased expression in esophageal mucosa GTEx Portal
  • HAGH (hydroxyacylglutathione hydrolase, which breaks down methylglyoxal, a toxic byproduct of glucose metabolism): increased expression in brain cerebellar hemisphere GTEx Portal
  • TELO2 (telomere maintenance 2, which helps coordinate the cellular DNA damage response): reduced expression in brain putamen, a basal ganglia structure involved in movement and reward learning GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What genes are near rs118002512?

rs118002512 sits in the HS3ST6-MSRB1 genomic region. HS3ST6 encodes an enzyme that adds sulfate groups to heparan sulfate, a sugar chain on cell surfaces that regulates interactions with growth factors. MSRB1 encodes a repair enzyme that restores oxidized methionine residues in proteins, protecting them from oxidative damage.

Which study identified rs118002512?

rs118002512 was identified in a genome-wide association study of 35 blood and urine biomarkers in the UK Biobank, covering more than 363,000 individuals and published in Nature Genetics in 2021.

What does IGFALS do?

IGFALS (Insulin-like Growth Factor Acid-Labile Subunit) is a protein that forms part of a complex in the blood that carries and stabilizes IGF-1, extending its circulation time. GTEx data show that rs118002512 is linked to increased IGFALS expression in brain and nerve tissues, though what this means for function or health is not established in the available studies.

Is rs118002512 linked to any disease?

The available study focused on blood and urine biomarker levels rather than disease diagnoses. No direct disease association for this specific variant is described in the provided study data.

Which tissues show altered gene expression at rs118002512?

GTEx data show expression effects in thyroid gland, non-sun-exposed skin, brain cerebellum, brain cerebellar hemisphere, tibial nerve, esophageal mucosa, and brain putamen, covering five genes: MEIOB, IGFALS, EME2, HAGH, and TELO2.