Expressive

rs11213921 (BTG4): Body Shape and Expression

Key takeaways

  • rs11213921 near BTG4 was found in a genome-wide study of body proportions in over 400,000 UK Biobank participants.
  • The locus falls among novel findings that included genes connected to morphogenesis, organogenesis, and cancer biology.
  • GTEx data show the variant increases expression of PPP2R1B in thyroid, two brain regions, and tibial artery.
  • The variant also increases expression of neighboring genes in spleen and tibial nerve.
  • Evidence for the body-shape association is preliminary; per-variant effect sizes were not available in the provided study materials.

Key takeaways

  • rs11213921 sits near the BTG4 gene and was identified through a large genome-wide study of allometric body-shape indices in over 406,000 UK Biobank participants.
  • The locus falls among novel findings in a GWAS that highlighted genes connected to morphogenesis, organogenesis, and cancer biology.
  • GTEx data show the alternative allele increases expression of PPP2R1B in thyroid, two brain regions, and tibial artery.
  • The variant also increases expression of neighboring genes in spleen and tibial nerve.
  • Evidence for the body-shape association is preliminary; per-variant effect sizes and p-values were not available in the provided study text.

What the research says A genome-wide association study of allometric body-shape indices (A Body Shape Index, ABSI; Hip Index, HI; and a calibrated Waist-to-Hip Index) was performed in 219,872 women and 186,825 men of white British ancestry from UK Biobank using Bayesian linear mixed models (BOLT-LMM), finding that one to two thirds of identified loci were novel, with many top-ranked regions containing genes tied to morphogenesis, organogenesis, and cancer-related processes. GTEx v11 eQTL data (953 donors, FDR < 0.05) for rs11213921 show consistent increases in PPP2R1B expression across thyroid (slope +0.68, p=1.2e-29), nucleus accumbens basal ganglia (slope +0.56, p=3.2e-11), caudate basal ganglia (slope +0.51, p=6.3e-11), and tibial artery (slope +0.34, p=5.0e-14), plus increased expression of ENSG00000307046 in thyroid and tibial nerve, and HOATZ and LAYN in spleen GTEx Portal.

Reported associations

  • Allometric body-shape indices (ABSI, HI, WHI): This variant was identified in a GWAS of allometric body-shape indices in UK Biobank (219,872 women and 186,825 men); no per-variant effect size or p-value was available in the provided study text.
  • PPP2R1B expression - thyroid: The alternative allele is associated with increased expression of PPP2R1B in thyroid (slope +0.68, p=1.2e-29) GTEx Portal.
  • PPP2R1B expression - brain basal ganglia: Increased expression in nucleus accumbens (slope +0.56, p=3.2e-11) and caudate (slope +0.51, p=6.3e-11) regions GTEx Portal.
  • PPP2R1B expression - tibial artery: Increased expression in tibial artery (slope +0.34, p=5.0e-14) GTEx Portal.
  • ENSG00000307046 expression - thyroid and tibial nerve: Increased expression in thyroid (slope +0.61, p=2.6e-20) and tibial nerve (slope +0.47, p=3.7e-11) GTEx Portal.
  • HOATZ expression - spleen: Increased expression in spleen (slope +0.88, p=1.8e-11) GTEx Portal.
  • LAYN expression - spleen: Increased expression in spleen (slope +0.63, p=2.1e-15) GTEx Portal.

Evidence quality The GWAS draws on a large sample of over 406,000 UK Biobank participants, with sex-stratified analyses and BOLT-LMM methodology suited to population-scale biobanks; the study reports that genetic associations were fewer in men than in women, and between one and two thirds of identified loci were novel compared to prior catalogs. However, the provided study text does not include a specific effect size, p-value, or replication entry for this variant, so the strength of evidence for its individual body-shape association cannot be precisely characterized from the available materials and should be treated as preliminary. The GTEx v11 eQTL signals for rs11213921 (953 donors, FDR < 0.05) are well-supported within that dataset across multiple distinct tissues, providing convergent mechanistic context, though eQTL data describe expression-level effects rather than direct trait associations.

Tissue-specific expression effects

  • PPP2R1B: Increased expression in thyroid, nucleus accumbens basal ganglia, caudate basal ganglia, and tibial artery in carriers of the alternative allele GTEx Portal.
  • ENSG00000307046: Increased expression in thyroid and tibial nerve GTEx Portal.
  • HOATZ: Increased expression in spleen GTEx Portal.
  • LAYN: Increased expression in spleen GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What does the BTG4 region have to do with body shape?

A genome-wide study of allometric body-shape indices in UK Biobank identified the BTG4 region as one of many novel loci. The study noted that many top-ranked regions contained genes linked to morphogenesis and organogenesis.

What is an allometric body shape index?

An allometric body shape index, such as the A Body Shape Index (ABSI) or Hip Index (HI), measures body proportions independently of both height and overall body size. Unlike simple waist or hip measurements, these indices account for how body dimensions scale with total body size.

Which tissues show expression effects for rs11213921?

According to GTEx data, rs11213921 is associated with increased expression of PPP2R1B in thyroid, nucleus accumbens, caudate basal ganglia, and tibial artery, and with increased expression of HOATZ and LAYN in spleen, and a neighboring gene in thyroid and tibial nerve.

What is PPP2R1B and why does it appear here?

PPP2R1B is a gene near this locus whose expression is consistently elevated by the alternative allele of rs11213921 across thyroid, brain basal ganglia regions, and tibial artery, according to GTEx eQTL data from 953 donors.

How strong is the evidence linking rs11213921 to body shape?

The parent GWAS used a large sample of over 406,000 participants and rigorous statistical methods, but specific effect sizes and p-values for this variant were not reported in the available study text. The association should be treated as preliminary pending independent replication.