rs10859481 (LINC02412-NUDT4): Athlete Metabolite Locus

Key takeaways

• rs10859481 was identified in a metabolomics genome-wide study of 490 elite athletes comparing genetic influences on metabolite levels
• GTEx data from 953 donors show this variant increases LINC02412 gene activity in coronary artery, subcutaneous adipose, and tibial artery tissue
• A nearby gene (ENSG00000257252) shows increased activity in heart atrial appendage, skin, and skeletal muscle linked to this variant
• Another nearby gene (ENSG00000293091) shows reduced activity in tibial nerve and subcutaneous adipose tissue
• Overall evidence is preliminary: the metabolomics association lacks a named metabolite in the available text and has not been independently replicated per the provided materials

What the research says rs10859481 was identified in a metabolic genome-wide association study (mGWAS, a large-scale scan linking genetic variants to metabolite levels in blood) conducted on 490 elite athletes, using 275,016 quality-controlled single-nucleotide polymorphisms (SNPs, single-letter DNA positions that vary between people) and serum profiling of 751 metabolites; the study compared metabolomics quantitative trait loci (mQTLs) in these athletes with previously published mQTLs from non-elite populations to uncover loci specific to or amplified in the high-performance athletic context, with particular focus on metabolites linked to endurance sports. The source publication does not include a PMID in the available metadata, limiting independent retrieval. Separately, GTEx eQTL (expression quantitative trait locus, a variant that influences how much a nearby gene is expressed) data from 953 donors identifies rs10859481 as influencing at least three genes across multiple tissue types, with all associations meeting a false discovery rate below 0.05 GTEx Portal.

Reported associations

• Metabolomics trait in elite athletes (mQTL): rs10859481 was identified in a mGWAS of 490 elite athletes comparing variant-metabolite associations in elite versus non-elite populations; the specific metabolite linked to this variant is not named in the provided study excerpt
• LINC02412 expression, coronary artery: the alternative allele associates with increased LINC02412 expression (slope +0.43, p=2.1e-7) in coronary artery tissue GTEx Portal
• LINC02412 expression, subcutaneous adipose tissue: increased LINC02412 expression (slope +0.38, p=5.9e-14) in subcutaneous fat tissue GTEx Portal
• LINC02412 expression, tibial artery: increased LINC02412 expression (slope +0.30, p=1.0e-9) in tibial artery tissue GTEx Portal
• ENSG00000293091 expression, tibial nerve: the alternative allele associates with decreased expression (slope -0.35, p=1.7e-10) in tibial nerve tissue GTEx Portal
• ENSG00000293091 expression, subcutaneous adipose: decreased expression (slope -0.31, p=1.5e-9) in subcutaneous fat tissue GTEx Portal
• ENSG00000257252 expression, heart atrial appendage: increased expression (slope +0.34, p=2.7e-9) in heart atrial appendage tissue GTEx Portal
• ENSG00000257252 expression, skin and skeletal muscle: increased expression in sun-exposed lower leg skin (slope +0.29, p=3.9e-12) and skeletal muscle (slope +0.26, p=5.1e-12) GTEx Portal

Evidence quality The mGWAS evidence rests on a single cohort of 490 elite athletes genotyped at 275,016 SNPs alongside 751 serum metabolites; no independent replication of the rs10859481-metabolite association is reported in the available study text, and the source publication has no recorded PMID in the provided metadata, which limits independent verification. The GTEx eQTL associations are better-powered, derived from 953 donors across a broad panel of tissue types, and each reported association clears a false discovery rate threshold below 0.05. The eQTL effects are mechanistic (they describe changes in gene activity, not health outcomes), so their clinical relevance cannot be established from the provided data alone. Taken together, evidence for this locus is preliminary: the metabolomics signal awaits replication and specific metabolite identification, while the expression data provide a tissue-resolved mechanistic picture whose downstream consequences remain unstated in the available sources.

Tissue-specific expression effects

• LINC02412: the alternative allele at rs10859481 associates with increased expression of this gene in coronary artery, subcutaneous adipose, and tibial artery tissue GTEx Portal
• ENSG00000293091: the alternative allele associates with reduced expression in tibial nerve and subcutaneous adipose tissue GTEx Portal
• ENSG00000257252: the alternative allele associates with increased expression in heart atrial appendage, sun-exposed lower leg skin, and skeletal muscle GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.