rs10487140 (PDK4-DYNC1I1): Athletic Metabolism
Key takeaways
- This variant near PDK4-AS1 and DYNC1I1 was identified in a metabolomics GWAS of 490 elite athletes.
- GTEx data show the alternate allele reduces DYNC1I1 expression in skeletal muscle and increases PDK4-AS1 expression in tibial nerve.
- The same variant increases PDK4 expression in fibroblasts and shows a very strong association with an uncharacterized gene in testis (p=2.7e-37).
- Evidence linking this locus to athletic performance comes from one preliminary study without documented independent replication.
- The molecular eQTL signals are statistically well-supported; their functional consequences in athletic or clinical contexts are not yet established.
Key takeaways
- This variant near PDK4-AS1 (an antisense RNA gene) and DYNC1I1 (a motor protein gene) was identified in a metabolomics genome-wide study of elite athletes investigating how genetic variants relate to athletic performance.
- GTEx expression data show the alternate allele is associated with reduced DYNC1I1 expression in skeletal muscle and increased PDK4-AS1 expression in tibial nerve.
- The alternate allele is also linked to increased expression of PDK4 (pyruvate dehydrogenase kinase 4) in cultured fibroblasts and a very strong increase in an uncharacterized gene's expression in testis (p=2.7e-37).
- These are preliminary findings from a single study of 490 athletes; independent replication is not documented in the available materials.
- The molecular eQTL signals are statistically well-supported; their functional consequences in athletic or clinical contexts are not yet established.
What the research says A metabolomics genome-wide association study (mGWAS) in 490 elite athletes sought to identify genetic variants influencing measured metabolite levels as intermediate markers of athletic performance, confirming 104 endurance-associated metabolites and identifying novel metabolic loci in genes including FOLH1, VNN1, and SULT2A1 (Al-Khelaifi et al., Scientific Reports, 2020). Separately, GTEx v11 expression data from 953 donors show this locus has measurable tissue-specific effects on the expression of multiple nearby genes, with signals ranging from tibial nerve (PDK4-AS1, p=1.6e-4) to skeletal muscle (DYNC1I1, p=4.1e-7) to testis (ENSG00000302505, p=2.7e-37) GTEx Portal.
Reported associations
- Athletic performance metabolomics: This locus was studied in an mGWAS of 490 elite athletes examining metabolites involved in fatty acid metabolism, steroid biosynthesis, and energy-related pathways (Al-Khelaifi et al., Scientific Reports, 2020).
- DYNC1I1 expression in skeletal muscle: The alternate allele is associated with reduced expression of DYNC1I1 (dynein cytoplasmic 1 intermediate chain 1) in skeletal muscle GTEx Portal.
- PDK4-AS1 expression in tibial nerve: The alternate allele is associated with increased expression of PDK4-AS1 in tibial nerve GTEx Portal.
- PDK4 expression in cultured fibroblasts: The alternate allele is associated with increased expression of PDK4 (pyruvate dehydrogenase kinase 4) in cultured fibroblasts GTEx Portal.
- ASB4 expression in brain regions: The alternate allele is associated with increased expression of ASB4 (ankyrin repeat and SOCS box protein 4) in cervical spinal cord (c-1) and hypothalamus GTEx Portal.
- ENSG00000302505 expression in testis: The alternate allele is associated with substantially increased expression of ENSG00000302505 (an uncharacterized locus as annotated in the source data) in testis, the strongest eQTL signal at this position (p=2.7e-37) GTEx Portal.
Evidence quality The athletic performance context comes from a single mGWAS cohort of 490 elite athletes - a modest sample for genome-wide work - and the source publication metadata does not include a PMID, limiting independent verification. No replication in a separate cohort is reported in the provided materials. The GTEx eQTL evidence (GTEx v11, n=953 donors, FDR<0.05) provides a more robustly powered molecular line of evidence: p-values range from 1.6e-4 for PDK4-AS1 in tibial nerve, to 4.1e-7 for DYNC1I1 in skeletal muscle, to 2.7e-37 for ENSG00000302505 in testis. The gene expression effects at the molecular level are well-supported statistically; the connection to athletic performance phenotypes should be treated as preliminary pending replication in independent cohorts.
Tissue-specific expression effects
- ENSG00000302505: The alternate allele is associated with strongly increased expression in testis GTEx Portal.
- ASB4: The alternate allele is associated with increased expression in cervical spinal cord (c-1) and hypothalamus GTEx Portal.
- DYNC1I1: The alternate allele is associated with reduced expression in skeletal muscle GTEx Portal.
- PDK4-AS1: The alternate allele is associated with increased expression in tibial nerve GTEx Portal.
- PDK4: The alternate allele is associated with increased expression in cultured fibroblasts GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What genes are near rs10487140?
rs10487140 sits near PDK4-AS1 (an antisense RNA gene), PDK4 (pyruvate dehydrogenase kinase 4), DYNC1I1 (dynein cytoplasmic 1 intermediate chain 1), ASB4 (ankyrin repeat and SOCS box protein 4), and an uncharacterized locus annotated ENSG00000302505. GTEx data show the variant affects expression of all of these genes across different tissues.
Is rs10487140 linked to athletic performance?
It was examined in a metabolomics GWAS of 490 elite athletes studying metabolic traits associated with endurance. These findings are preliminary, come from a single study without an independently verifiable publication identifier, and have not been replicated in the reviewed materials.
What does the GTEx data show for rs10487140?
GTEx v11 data from 953 donors show the alternate allele is associated with reduced DYNC1I1 expression in skeletal muscle, increased PDK4-AS1 expression in tibial nerve, increased PDK4 expression in fibroblasts, increased ASB4 expression in spinal cord and hypothalamus, and a very strong increase in ENSG00000302505 expression in testis (p=2.7e-37).
What is DYNC1I1 and why is its expression in muscle relevant?
DYNC1I1 (dynein cytoplasmic 1 intermediate chain 1) is a component of the dynein motor protein complex, which transports cargo along microtubules inside cells. GTEx data show this variant is associated with reduced DYNC1I1 expression specifically in skeletal muscle, though the functional consequences of this reduction are not described in the reviewed studies.
What is PDK4 and how does rs10487140 relate to it?
PDK4 (pyruvate dehydrogenase kinase 4) is an enzyme involved in energy metabolism. GTEx data show this variant is associated with increased PDK4 expression in cultured fibroblasts, and the locus also contains PDK4-AS1, an antisense RNA gene whose expression in tibial nerve is increased by the alternate allele.