rs11635717 (NR2F2-AS1): Elite Athlete Metabolic Variant

Key takeaways

• rs11635717 near NR2F2-AS1 was identified in the context of a metabolic genome-wide association study (GWAS) of 490 elite athletes
• GTEx data from 953 donors shows the variant is linked to increased NR2F2-AS1 expression in testis, tibial artery, tibial nerve, the heart's atrial appendage, and subcutaneous fat tissue
• A neighboring unannotated transcript (ENSG00000280048) shows reduced expression in tibial nerve tissue for the same allele
• Evidence is preliminary and comes from a single specialized athlete cohort with no published replication
• No specific lifestyle interventions are linked to this variant in the available evidence

What the research says The available GWAS context for rs11635717 comes from a study of 490 elite athletes that combined serum metabolomics profiling of 751 metabolites with genotyping of over 275,000 quality-controlled single nucleotide polymorphisms (SNPs), aimed at identifying genetically-influenced metabolites that distinguish elite from non-elite athletes; that study sought novel metabolic quantitative trait loci (mQTLs, meaning genetic variants linked to measurable metabolite levels) in athletes, with authors noting potential applications in biomarker discovery and therapeutic strategies, though the specific metabolite association for this locus is not detailed in the available study text. GTEx v11 eQTL data from 953 donors independently establishes that the alternate allele at this position increases expression of NR2F2-AS1 (the gene at this locus, designated by standard naming convention as an antisense RNA neighboring the NR2F2 gene) across multiple tissues, with the most pronounced signal in testis GTEx Portal.

Reported associations

• Metabolic trait in elite athletes: rs11635717 appears in the context of an mQTL study of 490 elite athletes; the specific metabolite linked to this locus is not detailed in the available study text
• NR2F2-AS1 expression (testis): the alternate allele is associated with increased expression, with testis showing the strongest effect among all tissues tested GTEx Portal
• NR2F2-AS1 expression (vascular and peripheral tissues): increased expression is also observed in tibial artery, tibial nerve, the heart's atrial appendage, and subcutaneous adipose tissue GTEx Portal
• ENSG00000280048 expression (tibial nerve): the alternate allele is associated with reduced expression of this neighboring unannotated transcript specifically in tibial nerve tissue GTEx Portal

Evidence quality The GWAS context derives from a single study of 490 elite athletes, a small and highly specialized cohort relative to population-level GWAS studies that typically enroll tens of thousands of participants; no replication in an independent athlete cohort is mentioned in the available study text, and no specific effect size or p-value for rs11635717's metabolic association could be confirmed from the provided excerpt. The GTEx eQTL findings draw on 953 donors across numerous tissue types, with statistically strong signals reaching approximately 1.4 x 10^-13 in testis for NR2F2-AS1 and approximately 1.2 x 10^-13 in tibial nerve for the neighboring transcript ENSG00000280048 GTEx Portal, providing substantially stronger statistical support for the tissue expression findings than for the metabolic GWAS association. Overall the evidence should be treated as preliminary.

Tissue-specific expression effects

• NR2F2-AS1: the alternate allele is associated with increased expression in testis (most pronounced effect), tibial artery, tibial nerve, the heart's atrial appendage, and subcutaneous adipose tissue GTEx Portal
• ENSG00000280048: the alternate allele is associated with reduced expression in tibial nerve tissue GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.