rs12280555 (CCDC81): Athlete Metabolomics Variant
Key takeaways
- rs12280555 near CCDC81 was studied in a metabolomics and genomics scan of 490 elite athletes, examining how genes shape blood metabolite levels
- GTEx data from 953 donors links this variant to reduced CCDC81 expression in 8 tissue types, including brain regions, thyroid, coronary artery, and visceral fat
- The strongest expression effects are in thyroid (p=3.4e-11) and frontal cortex (p=1.4e-10), both reaching high statistical significance
- Evidence for any specific metabolite association is preliminary; the athlete study was small for a GWAS and the exact metabolite link is not detailed in available text
Key takeaways
- rs12280555 near CCDC81 was studied in a metabolomics and genomics scan of 490 elite athletes, examining how genes shape blood metabolite levels
- GTEx data from 953 donors links this variant to reduced CCDC81 expression in 8 tissue types, including brain regions, thyroid, coronary artery, and visceral fat
- The strongest expression effects are in thyroid (p=3.4e-11) and frontal cortex (p=1.4e-10), both reaching high statistical significance
- Evidence for any specific metabolite association is preliminary; the athlete study was small for a GWAS and the exact metabolite link is not detailed in available text
What the research says A metabolomics genome-wide association study (mGWAS, a study combining genetic data with measurements of hundreds of small molecules in the blood) was conducted in 490 elite athletes, profiling 275,016 genetic variants alongside 751 serum metabolites to identify novel metabolic quantitative trait loci (mQTLs, genetic variants that influence metabolite levels in the blood). Expression data from the GTEx project (953 donors, cis-window analysis, FDR<0.05) shows that rs12280555 is associated with reduced expression of CCDC81 (coiled-coil domain containing 81) across eight tissue types, with the most statistically significant effects in thyroid tissue (p=3.4e-11) and frontal cortex brain tissue (p=1.4e-10) GTEx Portal. All eight reported tissue associations show the same direction of effect, suggesting a consistent cis-regulatory influence on this locus GTEx Portal.
Reported associations
- Metabolic trait in elite athletes: rs12280555 was investigated in a genome-wide metabolomics study of 490 elite athletes profiling 275,016 SNPs and 751 serum metabolites; the specific metabolite association for this variant is not detailed in the available study excerpt
- CCDC81 gene expression, 8 tissues (eQTL): the variant is consistently associated with reduced expression across coronary artery (slope -0.44, p=1.4e-5), brain cerebellum (slope -0.43, p=1.6e-5), thyroid (slope -0.41, p=3.4e-11), minor salivary gland (slope -0.41, p=3.9e-5), cerebellar hemisphere (slope -0.40, p=6.6e-6), frontal cortex BA9 (slope -0.40, p=1.4e-10), amygdala (slope -0.36, p=1.4e-5), and visceral omental fat (slope -0.33, p=2.3e-7), based on 953 donors GTEx Portal
Evidence quality The eQTL evidence from GTEx is well-powered at 953 donors, with two associations reaching p-values below 1e-9: thyroid (p=3.4e-11) and frontal cortex BA9 (p=1.4e-10), and all eight tissue associations meeting FDR<0.05 GTEx Portal. The consistent negative slope direction across all eight tissues strengthens the case for a genuine cis-regulatory effect at this locus. The elite athlete mGWAS (n=490) is relatively small for a genome-wide study of this type, and the available study text does not specify the individual metabolite or effect size attributable to rs12280555, making independent evaluation of that metabolite-genotype association's statistical strength impossible from the provided evidence. No PMID is listed for the athlete study in the provided metadata, and no replication study for the specific metabolite association is present in the available evidence. These limitations mean the metabolite association should be considered preliminary.
Tissue-specific expression effects
- CCDC81: reduced expression across eight tissues, including brain (frontal cortex, cerebellum, cerebellar hemisphere, and amygdala), thyroid, coronary artery, minor salivary gland, and visceral abdominal fat, with the strongest effects in thyroid and frontal cortex and a consistent negative direction across all tissues reported GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs12280555?
rs12280555 is a genetic variant located near the CCDC81 gene (coiled-coil domain containing 81). It has been investigated in metabolomics research on elite athletes and shows effects on CCDC81 gene expression in multiple tissue types.
What does rs12280555 do to CCDC81 gene expression?
GTEx data from 953 donors shows rs12280555 is associated with reduced CCDC81 expression in eight tissues: frontal cortex, cerebellum, cerebellar hemisphere, amygdala, thyroid, coronary artery, minor salivary gland, and visceral fat. All effects go in the same direction: reduced expression.
Is rs12280555 linked to athletic performance?
This variant was examined in a genome-wide metabolomics study of 490 elite athletes that identified genetic variants influencing metabolite levels. The study's specific metabolite finding for rs12280555 is not detailed in available evidence, so any link to athletic performance remains preliminary.
What tissues are affected by rs12280555?
GTEx data shows reduced CCDC81 expression in thyroid, frontal cortex (Brodmann area 9), cerebellum, cerebellar hemisphere, amygdala, coronary artery, minor salivary gland, and visceral omental fat.
What is a metabolic QTL (mQTL)?
A metabolic quantitative trait locus (mQTL) is a genetic variant that influences the level of a specific metabolite, a small molecule produced during metabolism. Identifying mQTLs in athlete populations can help researchers understand how genetic differences shape metabolic responses to exercise.