Expressive

rs1165200 (SLC17A3): Plasma Metabolomics Variant

Key takeaways

  • rs1165200 is a variant at the SLC17A3 locus identified in a genome-wide study of 1,091 plasma metabolites in 8,299 individuals
  • The alternate allele consistently increases expression of LINC02980, a non-coding RNA, across eight tissue types including skin, fat, and muscle
  • The strongest effect on LINC02980 expression appears in cultured fibroblasts, with slopes above +0.70 in five of the eight reported tissues
  • The metabolomics study used Mendelian Randomization to link metabolites to 12 diseases, including bone mineral density and inflammatory bowel disease
  • Specific metabolite associations for this variant are not named in the available study data

Key takeaways

  • rs1165200 is a variant at the SLC17A3 locus identified in a genome-wide study of 1,091 plasma metabolites in 8,299 individuals from the Canadian Longitudinal Study on Aging
  • The alternate allele consistently increases expression of LINC02980, a long intergenic non-coding RNA (a gene that produces RNA but no protein), across eight tissue types
  • The strongest expression-increasing effects appear in cultured fibroblasts, followed by sun-exposed skin, visceral adipose, and subcutaneous adipose tissue
  • The source metabolomics study used Mendelian Randomization to probe causal links between metabolites and 12 diseases, including bone mineral density and inflammatory bowel disease
  • Specific metabolite associations for this variant are not named in the available study text

What the research says A genome-wide association study (GWAS) of 1,091 plasma metabolites and 309 metabolite ratios in 8,299 participants from the Canadian Longitudinal Study on Aging identified 690 metabolites with associations at 248 loci, with 94 effector genes mapped for 109 metabolites using integrated metabolite-gene and expression data. Using Mendelian Randomization, a technique that uses genetic variants as natural experiments to test whether one biological measure causally influences another, the study estimated causal effects for 22 metabolites on 12 traits, with examples including orotate for estimated bone mineral density, alpha-hydroxyisovalerate for BMI, and ergothioneine for inflammatory bowel disease and asthma. GTEx v11 expression data from 953 donors shows that the alternate allele at this locus robustly increases expression of the nearby LINC02980 gene across eight tissue types, with slopes ranging from +0.57 in skeletal muscle to +0.90 in cultured fibroblasts GTEx Portal.

Reported associations

  • Plasma metabolome locus: This variant falls at the SLC17A3 locus, which was identified among 248 loci associated with one or more of 690 plasma metabolites in a GWAS of 8,299 participants; the specific metabolite(s) linked to this position are not named in the available study text
  • LINC02980 gene expression: The alternate allele acts as an eQTL (expression quantitative trait locus, meaning the allele influences how much RNA the LINC02980 gene produces) in eight tissues: cultured fibroblasts, sun-exposed lower-leg skin, visceral adipose tissue, subcutaneous adipose tissue, esophagus mucosa, tibial nerve, unexposed suprapubic skin, and skeletal muscle, with increased expression in all eight GTEx Portal

Evidence quality The metabolomics GWAS applied a conservative p-value threshold of 6.85x10-10, corrected for 73 effective independent metabolites via Bonferroni adjustment, across 8,299 CLSA participants, with no detected population stratification or test-statistic inflation (max genomic inflation factor lambda 1.03). GTEx eQTL evidence for LINC02980 is based on 953 donors with FDR<0.05 in all eight reported tissues; slopes are uniformly positive, ranging from +0.57 to +0.90, indicating a consistent regulatory relationship across tissue types. No conflicting findings are present in the provided sources. The specific metabolite associated with this locus is not detailed in the available study excerpt, limiting interpretation of the downstream metabolic mechanism.

Tissue-specific expression effects

  • LINC02980: The alternate allele is associated with increased expression across all eight reported tissues, with the largest effect in cultured fibroblasts and consistent increases in skin (both sun-exposed and unexposed), visceral and subcutaneous adipose tissue, esophagus mucosa, tibial nerve, and skeletal muscle GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs1165200?

rs1165200 is a common genetic variant at the SLC17A3 locus. It was identified in a large genome-wide study of over 1,000 plasma metabolites and is associated with increased expression of a nearby non-coding RNA called LINC02980 in multiple tissue types.

What gene is rs1165200 associated with?

rs1165200 is assigned to the SLC17A3 locus. GTEx v11 data from 953 donors also shows the variant acts as an expression quantitative trait locus for LINC02980, a nearby long intergenic non-coding RNA, in eight tissue types.

What is LINC02980 and why does rs1165200 affect its expression?

LINC02980 is a long intergenic non-coding RNA, a type of gene that produces RNA molecules rather than proteins. GTEx v11 data shows the alternate allele of rs1165200 consistently increases LINC02980 expression across eight tissues, suggesting this variant sits in or near a regulatory region of the genome.

Which tissues show expression changes linked to rs1165200?

GTEx v11 links rs1165200 to increased LINC02980 expression in cultured fibroblasts, sun-exposed skin, visceral and subcutaneous adipose tissue, esophagus mucosa, tibial nerve, unexposed skin, and skeletal muscle. All eight reported tissues show the same direction of effect.

Is rs1165200 linked to any disease?

The metabolomics GWAS that identified this locus examined causal links between metabolites and 12 conditions including bone mineral density, BMI, heart disease, and inflammatory bowel disease. A specific disease association for rs1165200 itself is not described in the available study data.