rs11011112 (LINC00993): Elite Athlete Metabolomics

Key takeaways

• rs11011112 lies within LINC00993, a long intergenic non-coding RNA gene, and was identified in a metabolomics study of 490 elite athletes
• GTEx data (953 donors, FDR below 0.05) links the ALT allele to altered expression of five nearby genes across testis, lung, and esophagus
• The strongest expression signal is in testis, where three separate nearby genes show changed activity
• Evidence for this variant's metabolite associations is preliminary, from a single study with a modest sample size and no reported independent replication
• The non-coding RNA location makes the biological mechanism of any functional effect uncertain

What the research says rs11011112 sits within LINC00993 and was examined in a metabolic genome-wide association study (mGWAS, a statistical scan of hundreds of thousands of genetic variants for links to measured metabolites) conducted in 490 elite athletes using 751 serum metabolites and 275,016 quality-controlled SNPs; the study authors describe it as the first report of common variant metabolic quantitative trait loci (mQTLs, genetic positions that statistically predict metabolite concentrations) linked to elite athletic performance and endurance sports. That study compared mQTLs identified in athletes against reference data from non-athlete populations to find performance-relevant metabolite links, with the specific metabolite association for this locus not detailed in the available text. Separately, tissue-level expression data from GTEx v11 shows the ALT allele of this variant is associated with altered expression of five nearby genes in testis, lung, and esophageal tissue GTEx Portal.

Reported associations

• Athletic performance metabolomics: Identified in a metabolic GWAS of 490 elite athletes profiling 751 serum metabolites; the specific metabolite linked to this variant is not detailed in the available study text
• Testis gene expression (ENSG00000304597): The ALT allele is associated with reduced expression of this gene in testis (p=8.0e-14) GTEx Portal
• Testis gene expression (ENSG00000290801): The ALT allele is associated with increased expression of this gene in testis (p=2.5e-6) GTEx Portal
• Testis gene expression (ENSG00000225965): The ALT allele is associated with increased expression of this gene in testis (p=4.0e-4) GTEx Portal
• Lung gene expression (ZNF33BP1): The ALT allele is associated with reduced expression of ZNF33BP1, a zinc finger protein-coding gene, in lung tissue (p=1.9e-4) GTEx Portal
• Esophageal gene expression (ZNF33A): The ALT allele is associated with reduced expression of ZNF33A, another zinc finger protein-coding gene, at the gastroesophageal junction (p=1.9e-4) GTEx Portal

Evidence quality The primary published evidence for this variant's metabolite relevance comes from a single mGWAS in 490 elite athletes, which is a modest sample for a genome-wide study; large GWAS typically enroll tens of thousands to hundreds of thousands of participants. No independent replication cohort is described in the available text, and the specific effect size and significance threshold for rs11011112's metabolite association are not provided in the available excerpt. The GTEx eQTL signals are better characterized: the testis signal for ENSG00000304597 reaches p=8.0e-14 and the signal for ENSG00000290801 reaches p=2.5e-6 GTEx Portal, while the remaining three eQTL signals fall near p=1.9e-4 to p=4.0e-4, all passing a FDR threshold below 0.05 across 953 donors. Overall, the expression associations are the better-supported findings; the metabolomics context is preliminary.

Tissue-specific expression effects

• ENSG00000304597: Reduced expression in testis GTEx Portal
• ENSG00000290801: Increased expression in testis GTEx Portal
• ENSG00000225965: Increased expression in testis GTEx Portal
• ZNF33BP1: Reduced expression in lung GTEx Portal
• ZNF33A: Reduced expression in esophagus at the gastroesophageal junction GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.