Expressive

rs10852797 (FOXK2): Height-Associated Genetic Variant

Key takeaways

  • rs10852797 is one of 12,111 common SNPs linked to adult height in a genome-wide study of 5.4 million people across five ancestry groups.
  • The full set of height-linked SNPs from that study collectively explains roughly 40% of height variation in European-ancestry populations, and 10-24% in other ancestry groups.
  • The alternate allele increases FOXK2 gene activity in skeletal muscle, the strongest eQTL signal at this locus.
  • A second gene at this locus (ENSG00000308980) also shows increased activity in aortic artery tissue when this allele is present.

Key takeaways

  • rs10852797 is one of 12,111 common SNPs linked to adult height in a genome-wide study of 5.4 million people across five ancestry groups.
  • The full set of height-linked SNPs from that study collectively explains roughly 40% of height variation in European-ancestry populations, and 10-24% in other ancestry groups.
  • The alternate allele increases FOXK2 gene activity in skeletal muscle, the strongest eQTL signal at this locus.
  • A second gene at this locus (ENSG00000308980) also shows increased activity in aortic artery tissue when this allele is present.

What the research says rs10852797, in the FOXK2 gene region, is among the 12,111 independent SNPs identified as significantly associated with adult height in a meta-analysis of 5,380,080 individuals drawn from 281 studies across five major ancestry groups; those variants cluster in 7,209 non-overlapping genomic segments covering roughly 21% of the genome and collectively account for approximately 40% of height phenotypic variance in European-ancestry populations. Tissue-level data from GTEx v11 (953 donors, FDR below 0.05, meaning fewer than 5% of listed associations are expected to be false positives) show that the alternate allele acts as an eQTL (a variant that influences how much a nearby gene is expressed): it is linked to increased FOXK2 expression in skeletal muscle (slope +0.11, p=1.2e-12) and cultured fibroblasts (slope +0.09, p=1.1e-4), and to increased expression of a second gene at this locus, ENSG00000308980, in aortic artery tissue (slope +0.26, p=8.2e-5) GTEx Portal.

Reported associations

  • Adult height: rs10852797 is among 12,111 independent height-associated SNPs in a meta-analysis of 5,380,080 individuals across five ancestry groups; the full SNP set accounts for roughly 40% of height phenotypic variance in European-ancestry populations and 10-24% in other populations.
  • FOXK2 expression in skeletal muscle: The alternate allele is linked to increased FOXK2 activity (slope +0.11, p=1.2e-12, FDR below 0.05) GTEx Portal.
  • FOXK2 expression in cultured fibroblasts: The alternate allele is linked to increased FOXK2 activity (slope +0.09, p=1.1e-4, FDR below 0.05) GTEx Portal.
  • ENSG00000308980 expression in aortic artery tissue: The alternate allele is linked to increased ENSG00000308980 activity (slope +0.26, p=8.2e-5, FDR below 0.05) GTEx Portal.

Evidence quality The height association evidence comes from a very large meta-analysis (n=5,380,080 across 281 studies), providing strong statistical power for discovery. Effect size estimates and gene-prioritization patterns are broadly consistent across the five ancestry groups studied, but prediction accuracy is notably lower in non-European ancestry populations (10-24% of variance) than in European-ancestry populations (40-45%), a gap the study attributes to differences in linkage disequilibrium (the tendency of nearby genetic variants to be inherited together as a block) and allele frequency rather than to differences in the underlying biology. The individual contribution of rs10852797 to height variance is not broken out in the study text available here; it is one of 12,111 contributing SNPs whose per-SNP effect sizes are not individually reported in the provided data. For the eQTL associations, the FOXK2-skeletal muscle signal is the strongest (p=1.2e-12), while the fibroblast signal (p=1.1e-4) and the ENSG00000308980 aortic artery signal (p=8.2e-5) are weaker but still pass the FDR threshold; all three should be considered preliminary regulatory evidence rather than established clinical findings GTEx Portal.

Tissue-specific expression effects

  • FOXK2: The alternate allele is associated with increased expression in skeletal muscle (stronger signal, p=1.2e-12) and in cultured fibroblasts (weaker signal, p=1.1e-4) GTEx Portal.
  • ENSG00000308980: The alternate allele is associated with increased expression in aortic artery tissue (p=8.2e-5) GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

Is rs10852797 linked to human height?

Yes. This variant is among 12,111 independent SNPs significantly associated with adult height in a meta-analysis of 5,380,080 individuals across five ancestry groups. The full set of height-linked SNPs explains roughly 40% of height variation in European-ancestry populations and 10-24% in other ancestry populations.

What does the FOXK2 gene do?

The studies available for this entry do not describe the biological function of FOXK2 in detail. What is established is that rs10852797 sits in the FOXK2 region, is associated with adult height, and the alternate allele is linked to increased FOXK2 gene activity in skeletal muscle and cultured fibroblasts.

What is an eQTL and why does it matter here?

An eQTL, or expression quantitative trait locus, is a genetic variant statistically linked to differences in how much a nearby gene is expressed in a specific tissue. For rs10852797, the alternate allele is associated with higher FOXK2 activity in skeletal muscle and cultured fibroblasts, suggesting the variant may influence gene regulation in those tissues, though eQTL effects describe a mechanism rather than a clinical outcome.

Does this variant work the same way in all ancestry groups?

Effect size estimates and gene-prioritization patterns for height are broadly consistent across the five ancestry groups studied. However, the ability to predict height from common variants including this one is lower in non-European ancestry populations (10-24% of variance explained) than in European-ancestry populations (40-45%), a gap attributed to differences in how nearby variants are inherited together in different populations rather than to differences in causal biology.

What is ENSG00000308980?

ENSG00000308980 is an Ensembl gene identifier for a second gene at the rs10852797 locus whose expression is influenced by the alternate allele, specifically in aortic artery tissue. The data available for this entry do not provide a common name for this gene.