Expressive

rs11950938 (NSD1): Adult Height Variant

Key takeaways

  • rs11950938 is one of 697 genome-wide significant variants for adult height found in 253,288 people
  • These 697 variants together explain about one-fifth of the inherited variation in height
  • The alt allele raises FGFR4 expression (a fibroblast growth factor receptor) in testis and thyroid
  • The alt allele also raises RAB24 expression in nerve, aortic tissue, and skin
  • All participants were of European ancestry, so findings may not generalize equally to other populations

Key takeaways

  • rs11950938, at the NSD1 (nuclear receptor binding SET domain protein 1) locus, was identified as one of 697 genome-wide significant variants for adult height in a study of 253,288 individuals
  • These 697 variants cluster across 423 genomic loci and together explain approximately one-fifth of the inherited variation in height
  • The alt allele at this position is associated with increased expression of FGFR4 (a fibroblast growth factor receptor) in testis and thyroid tissue
  • The alt allele is also associated with increased expression of RAB24 in tibial nerve, aortic tissue, and lower leg skin
  • Evidence is drawn from European-ancestry individuals only, limiting what can be inferred about other populations

What the research says rs11950938 was identified as a genome-wide significant variant (P < 5x10-8) for adult human height in a GWAS meta-analysis of 253,288 European-ancestry individuals across 79 studies; the 697 total genome-wide significant variants from that study clustered across 423 loci and together explained approximately one-fifth of the heritable component of height, with all common variants collectively accounting for roughly 60% of heritability. Fibroblast growth factor signaling was among the biological pathways explicitly highlighted as enriched within these height-associated loci. GTEx eQTL data (953 donors, FDR < 0.05) shows the alt allele is associated with increased FGFR4 expression in testis and thyroid, and increased RAB24 expression in tibial nerve, aortic tissue, and lower leg skin GTEx Portal.

Reported associations

  • Adult height: rs11950938 was among 697 variants at genome-wide significance for adult height in a 253,288-person GWAS meta-analysis; these 697 variants collectively explain approximately one-fifth of the heritable component of height
  • FGFR4 expression: The alt allele is associated with increased FGFR4 expression in testis and thyroid tissue GTEx Portal
  • RAB24 expression: The alt allele is associated with increased RAB24 expression in tibial nerve, aortic tissue, and sun-exposed lower leg skin GTEx Portal

Evidence quality The height association comes from a large GWAS meta-analysis of 253,288 European-ancestry individuals across 79 studies. Among the 403 of the 697 genome-wide significant variants testable on an independent Metabochip array panel (n = 80,067 individuals across 37 studies), directional consistency exceeded 99% and effect size concordance was highly significant (P = 1.9x10-160). The analysis used GCTA-based conditional and joint multiple-SNP methods to account for linkage disequilibrium between variants. All participants were of European ancestry, which limits generalizability to other populations. The eQTL data from GTEx (953 donors, FDR < 0.05) reflects tissue-specific expression differences and does not constitute clinical outcome evidence. The individual variance contribution of this specific variant was not isolated in the provided study text.

Tissue-specific expression effects

  • FGFR4: The alt allele is associated with increased expression in testis and thyroid; fibroblast growth factor signaling was explicitly identified as one of the biological pathways enriched among height-associated loci in the GWAS GTEx Portal
  • RAB24: The alt allele is associated with increased expression in tibial nerve, aortic tissue, and sun-exposed lower leg skin GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs11950938?

rs11950938 is a common genetic variant at the NSD1 locus. It was identified as one of 697 variants associated with adult height at genome-wide significance in a study of 253,288 individuals.

What does the NSD1 gene do?

NSD1 (nuclear receptor binding SET domain protein 1) is the gene at this chromosomal locus. Common variants near NSD1 have been linked to variation in adult height in large genome-wide association studies.

Is rs11950938 linked to height?

Yes. A genome-wide association study of 253,288 European-ancestry individuals identified rs11950938 as one of 697 variants associated with adult height at genome-wide significance. These variants together explain roughly one-fifth of the inherited component of height variation.

What is FGFR4 and how does it relate to this variant?

FGFR4 is fibroblast growth factor receptor 4. GTEx data shows the alt allele of rs11950938 is associated with increased FGFR4 expression in testis and thyroid, and fibroblast growth factor signaling was highlighted as a pathway enriched among height-associated loci in the same genome-wide study.

What is RAB24 and how is it connected to rs11950938?

RAB24 is a gene near the NSD1 locus whose expression is influenced by rs11950938. GTEx data shows the alt allele is associated with increased RAB24 expression in tibial nerve, aortic tissue, and sun-exposed lower leg skin, though the relationship between this expression change and height variation is not directly established by the available data.