Expressive

rs10762269 (HKDC1): Body Composition eQTL Variant

Key takeaways

  • rs10762269 is an eQTL for HKDC1, linked to higher gene expression in 8 tissues including whole blood (p = 5.6e-19, n = 953 donors).
  • The increased-expression signal is consistent in direction across all 8 tissues studied in GTEx v11.
  • Genomic research has identified a neural-tissue-enriched genetic component underlying adiposity, providing context for signals at this locus.
  • Multivariate analyses of birth traits including head circumference have mapped signals in this genomic region.
  • Direct phenotypic effect sizes for this specific variant are not available in the current supplied study evidence.

Key takeaways

  • rs10762269 is an eQTL (expression quantitative trait locus) for HKDC1, meaning carriers of the alternate allele consistently show higher HKDC1 expression across multiple tissue types.
  • The alternate allele is linked to increased HKDC1 expression in 8 tissues, with the strongest statistical signal in whole blood (p = 5.6e-19, n = 953 donors).
  • Genomic research has characterized adiposity genetics into distinct factors, with the overall adiposity component enriched in neural tissues, providing research context for this locus.
  • Integrative GWAS analyses of infant head circumference and related birth traits have mapped signals in this genomic neighborhood.
  • The eQTL evidence is statistically robust; direct phenotypic effect sizes for this specific variant are not available in the supplied study text.

What the research says GTEx v11 data (953 donors, cis-window, FDR < 0.05) shows the alternate allele of rs10762269 is linked to higher HKDC1 expression across 8 tissues, with the strongest signal in whole blood (slope +0.32, p = 5.6e-19) and the largest magnitude effect in spleen (slope +0.38, p = 3.0e-7) GTEx Portal. A 4-factor genomic structural equation model (Genomic SEM) built from 18 anthropometric measures identified distinct genetic components for birth size, abdominal size, adipose distribution, and adiposity, finding the adiposity factor specifically enriched in neural tissues and pathways, with polygenic scores derived from it predicting multiple adverse health outcomes. Separately, multivariate GWAS analysis integrating infant head circumference (n = 10,768), birth length (n = 28,459), and birth weight (n = 143,677) has been applied to map genomic loci relevant to early growth traits, which carry heritability estimates around 0.23 for head circumference and are associated with later intelligence and mental health phenotypes.

Reported associations

  • Adiposity (latent genetic factor): A 4-factor Genomic SEM of 18 anthropometric measures identified a genetic component specific to overall adiposity, enriched in neural tissue pathways; polygenic scores derived from this factor predicted multiple adverse health outcomes, distinct from those derived from body size or fat distribution components.
  • Abdominal size and adipose distribution: The same modeling framework separated adipose distribution from overall adiposity, showing broader enrichment across physiological systems for distribution compared to adiposity; the alleles associated with higher subcutaneous-to-visceral adipose distribution were noted to be protective for cardiometabolic conditions.
  • Infant head circumference (birth anthropometrics): Integrative GWAS methods combining head circumference (n = 10,768), birth length (n = 28,459), and birth weight (n = 143,677) have mapped signals in this genomic neighborhood; head circumference has heritability approximately 0.23 (s.e. 0.05) and is associated with intelligence, autism, and other mental health-related conditions in later life.

Evidence quality The GTEx eQTL evidence for rs10762269 is statistically strong across all 8 tissues: whole blood p = 5.6e-19, thyroid p = 7.2e-13, pituitary p = 3.2e-8, and spleen p = 3.0e-7, all in 953 donors at FDR < 0.05, and all showing the same direction of effect GTEx Portal. The two studies providing phenotypic context - Arehart et al. (Nature Communications, 2025) on genomic architecture of adiposity, and Yang et al. (Frontiers in Genetics, 2020) on infant head circumference - do not carry explicit PMIDs in the provided metadata, and the supplied text covers introductory and methods material rather than variant-level association results; accordingly, direct effect sizes for rs10762269 on body composition or birth traits cannot be cited from these sources. The phenotypic associations are therefore preliminary research context for this locus rather than confirmed findings for this specific variant.

Tissue-specific expression effects

  • HKDC1: The alternate allele is associated with increased expression across spleen, whole blood, prostate, pituitary, adrenal gland, breast mammary tissue, stomach, and thyroid; the direction of effect is consistently upward across all 8 tissues, with the most statistically significant signal in whole blood and the second-most significant in thyroid GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs10762269?

rs10762269 is a single nucleotide polymorphism (a one-letter change in DNA) located near the HKDC1 gene. Population-level data from GTEx v11 shows that carriers of the alternate allele tend to have higher HKDC1 gene expression across multiple tissues.

What does the HKDC1 gene do?

HKDC1 is a gene at this locus whose expression is influenced by rs10762269 in at least 8 tissues, including whole blood, spleen, and pituitary gland. The downstream health implications of differences in its expression level remain under active study.

Is rs10762269 linked to obesity or body composition?

This variant sits in a genomic region studied in multivariate analyses of body composition. Research using genomic structural equation modeling identified distinct genetic factors for adiposity and fat distribution, with the adiposity factor enriched in neural tissues; however, explicit association evidence directly linking rs10762269 to those factors is not available in the current study text.

In which tissues does rs10762269 affect gene expression?

GTEx v11 data shows the alternate allele is associated with increased HKDC1 expression in 8 tissues: whole blood, spleen, prostate, pituitary, adrenal gland, breast mammary tissue, stomach, and thyroid. The effect is in the same direction - increased expression - across all 8 tissues.

How strong is the evidence for rs10762269?

The eQTL evidence from GTEx v11 is statistically robust, with the whole-blood signal reaching p = 5.6e-19 in 953 donors. Evidence for direct associations with body composition or birth traits is preliminary, as the studies provided do not include explicit effect sizes for this specific variant.