Expressive

rs1171652 (SLC16A9): UK Biobank Biomarker Locus

Key takeaways

  • rs1171652 sits near SLC16A9 (MCT9), a gene for a monocarboxylate transporter protein that moves small organic molecules across cell membranes
  • A 363,228-person UK Biobank study of 35 clinical lab tests identified this locus among 1,857 genome-wide significant hits with strict statistical thresholds
  • The alternative allele is linked to higher SLC16A9 activity in fibroblasts and esophageal tissue, per GTEx v11 data from 953 donors
  • The study cross-validated findings across multiple ancestry groups and benchmarked against 42 previously published cohorts

Key takeaways

  • rs1171652 is a variant near SLC16A9 (also called MCT9, or Monocarboxylate Transporter 9), a gene encoding a protein that moves small organic molecules such as monocarboxylates across cell membranes
  • A genome-wide association study of 35 standard blood and urine biomarkers in 363,228 UK Biobank participants identified this locus among 1,857 significant loci with 3,374 fine-mapped associations
  • The alternative allele at this position is linked to higher SLC16A9 expression in cultured fibroblasts and esophageal mucosa, based on GTEx v11 reference data from 953 donors
  • The study applied strict Bonferroni-corrected significance thresholds (p < 5 x 10^-9) and cross-validated findings across multiple ancestry groups
  • No lifestyle considerations have been recorded for this variant in the available evidence

What the research says A 2021 genome-wide association study in the UK Biobank scanned 35 standard clinical laboratory measurements - covering markers of kidney function, liver function, lipid levels, and glycemic traits - in 363,228 participants and identified 1,857 significantly associated loci with 3,374 fine-mapped associations; rs1171652, near SLC16A9 (MCT9), was among the loci identified at genome-wide significance. The study also applied Mendelian Randomization to uncover 51 causal relationships between biomarkers and clinical outcomes, including previously established effects of urate on gout and cystatin C on stroke risk, providing a broader framework for interpreting how loci in this class may affect health through biomarker levels. In GTEx v11 data (953 donors), the alternative allele at this locus is associated with increased SLC16A9 expression in cultured fibroblasts (eQTL slope +0.24, p = 4.8 x 10^-6) and esophageal mucosa (eQTL slope +0.15, p = 2.2 x 10^-5), indicating the variant modulates transporter gene output in at least two tissue types GTEx Portal.

Reported associations

  • Blood or urine biomarker (UK Biobank 35-panel): Identified at genome-wide significance (Bonferroni-corrected p < 5 x 10^-9) in a GWAS of 35 standard clinical laboratory measurements in 363,228 participants; the specific biomarker within this panel is not detailed in the available study excerpt
  • SLC16A9 expression in cultured fibroblasts: The alternative allele is linked to increased expression (eQTL slope +0.24, p = 4.8 x 10^-6) in GTEx v11 (953 donors) GTEx Portal
  • SLC16A9 expression in esophageal mucosa: The alternative allele is linked to increased expression (eQTL slope +0.15, p = 2.2 x 10^-5) in GTEx v11 (953 donors) GTEx Portal

Evidence quality The primary association evidence comes from Sinnott-Armstrong et al. (2021, Nature Genetics), a GWAS of 363,228 UK Biobank participants spanning White British (n=318,953), non-British White (n=23,582), African (n=6,019), South Asian (n=7,338), and East Asian (n=1,082) groups, with a cross-ancestry meta-analysis covering 355,891 individuals. Study-wide significance thresholds were Bonferroni-corrected at p < 5 x 10^-9 for assayed and imputed variants and p < 1 x 10^-6 for copy number variants. Linkage disequilibrium score regression intercepts ranged from 0.999 to 1.137 across all 35 traits, consistent with well-controlled population stratification. Effect sizes for 25 of the 35 biomarkers were benchmarked against 42 previously published cohorts and showed high overall agreement, supporting the robustness of the locus discovery. No specific p-value or effect size for rs1171652 individually is included in the available study excerpt. The GTEx v11 eQTL evidence is derived from 953 donors with FDR < 0.05 applied within the cis-window GTEx Portal. Overall, evidence quality is high for the general locus given the large sample and multi-ancestry design, though the absence of specific per-variant statistics in the excerpt limits granular interpretation.

Tissue-specific expression effects

  • SLC16A9: The alternative allele is associated with increased expression in both cultured fibroblasts (slope +0.24, the stronger of the two tissue effects) and esophageal mucosa (slope +0.15); both associations meet FDR < 0.05 in GTEx v11 cis-eQTL analysis across 953 donors 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.

Diet

  • limit high-purine foods Moderate

    Dietary purines are metabolized to urate; reducing intake helps moderate genetic predisposition to hyperuricemia

    Limit red meat, organ meats, and purine-rich seafood; prioritize plant-based proteins

  • sugar-sweetened beverages high in fructose Moderate

    Fructose metabolism increases urate production; this is particularly important with genetic predisposition

    Eliminate or greatly reduce sodas, fruit juices, and sweetened drinks

Lifestyle

  • alcohol moderation Moderate

    Alcohol impairs renal urate excretion and increases urate production; limiting intake is protective

    Limit to <=1 drink/day for women, <=2 for men

Screening

  • serum uric acid monitoring Moderate

    SLC16A9 rs1171652 is associated with higher urate levels; monitoring identifies hyperuricemia before clinical manifestation

    Check serum urate at baseline and annually during routine labs; escalate if >6.8 mg/dL

Frequently asked questions

What does the SLC16A9 gene do?

SLC16A9, also known as MCT9 (Monocarboxylate Transporter 9), encodes a protein that moves small organic molecules called monocarboxylates across cell membranes. It is part of the solute carrier family, a broad group of transporter proteins that regulate what enters and leaves cells.

What is rs1171652 associated with?

rs1171652 was identified at genome-wide significance in a large UK Biobank study of 35 standard blood and urine biomarkers in over 363,000 people. GTEx reference data also shows that the alternative allele is linked to higher expression of the nearby SLC16A9 gene in fibroblasts and esophageal tissue.

How large was the study that found rs1171652?

The primary study included 363,228 UK Biobank participants from multiple ancestry groups. It examined 35 standard clinical laboratory measurements and identified 1,857 significantly associated genetic loci across all 35 biomarkers, with 3,374 fine-mapped associations in total.

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 expressed in a given tissue. For rs1171652, GTEx v11 data shows the alternative allele is associated with higher SLC16A9 expression in cultured fibroblasts and esophageal mucosa, pointing to a potential mechanism through which the variant may affect biology.

Is rs1171652 linked to any disease?

The available evidence links rs1171652 to one or more blood or urine biomarkers measured in the UK Biobank. The same study used Mendelian Randomization to connect various biomarkers to outcomes such as gout and stroke risk, but no direct disease association for this specific variant is described in the available study data.