Expressive

rs10906982 (ADAMTSL3): Adult Height Variant

Key takeaways

  • rs10906982 is located near ADAMTSL3, an extracellular matrix gene that research has linked to human growth and development
  • Two independent genome-wide association studies connect this locus to adult height, reaching p-values from suggestive to genome-wide significant
  • Combining 20 identified height variants including this locus explains approximately 3% of height variation; a roughly 5 cm height gap separates individuals at the allele-count extremes
  • GTEx expression data show the alternative allele reduces expression of UBE2Q2P1 in seven tissues and reduces expression of a second gene in brain nucleus accumbens
  • Evidence comes primarily from European-ancestry cohorts; replication in diverse populations for this specific locus is incomplete

Key takeaways

  • rs10906982 is located near ADAMTSL3, an extracellular matrix gene that research has linked to human growth and development
  • Two independent genome-wide association studies connect this locus to adult height, reaching p-values from suggestive to genome-wide significant
  • Combining 20 identified height variants including this locus explains approximately 3% of height variation; a roughly 5 cm height gap separates individuals at the allele-count extremes
  • GTEx expression data show the alternative allele reduces expression of UBE2Q2P1 in seven tissues and reduces expression of a second gene in brain nucleus accumbens
  • Evidence comes primarily from European-ancestry cohorts; replication in diverse populations for this specific locus is incomplete

What the research says

A two-stage GWAS of 30,147 European-ancestry participants (13,665 discovery-phase, 16,482 follow-up) identified ADAMTSL3 - an extracellular matrix gene - as one of 20 loci associated with adult height (P < 5 x 10^-7); those 20 variants combined explain approximately 3% of height variation, with a roughly 5 cm height gap between the 6.2% of individuals carrying 17 or fewer tall alleles and the 5.5% carrying 27 or more PMID 18391952. An independent GWAS in 11,536 Australian twins and family members found suggestive evidence (P < 1 x 10^-6) at the same locus, with height-associated variants in that study collectively explaining less than 2% of phenotypic variation PMID 20397782. GTEx eQTL data additionally link the alternative allele at this position to reduced expression of UBE2Q2P1 across seven tissues and to reduced expression of ENSG00000291062 in brain nucleus accumbens basal ganglia, pointing to regulatory effects beyond the height phenotype GTEx Portal.

Reported associations

  • Adult height - two-stage European GWAS (n=30,147): The ADAMTSL3 locus reached genome-wide significance (P < 5 x 10^-7); 20 height loci combined explain approximately 3% of height variance, corresponding to a roughly 5 cm range across allele-count extremes PMID 18391952
  • Adult height - Australian twin cohort (n=11,536): Suggestive association (P < 1 x 10^-6) at this locus; height-associated variants from that analysis collectively explain less than 2% of phenotypic height variation PMID 20397782

Evidence quality

Two independent GWAS support the height association at the ADAMTSL3 locus. Weedon et al. used a two-stage design in 30,147 European-ancestry individuals and cleared a genome-wide significance threshold (P < 5 x 10^-7); the study adjusted for population stratification using EIGENSTRAT and reported a genomic control inflation factor of 1.12, indicating well-controlled type-1 error risk PMID 18391952. Liu et al. found only suggestive significance (P < 1 x 10^-6) in a smaller cohort, reflecting lower statistical power PMID 20397782. Both reports are restricted to European-ancestry samples. The PAGE consortium GWAS (n=49,839 non-European participants spanning Hispanic/Latino, African American, Asian, and Native Hawaiian ancestries) demonstrated that effect sizes and allele frequencies can differ substantially across populations and that associations discovered in European cohorts may not extrapolate directly to other groups PMID 31217584; no PAGE result specific to this locus appeared in the text reviewed. No conflicting findings among the three studies were identified.

Tissue-specific expression effects

  • UBE2Q2P1: The alternative allele is associated with reduced expression in seven tissues: esophagus gastroesophageal junction, esophagus muscularis, adipose subcutaneous, lung, nerve tibial, cultured fibroblasts, and skin (sun-exposed lower leg) GTEx Portal
  • ENSG00000291062: The alternative allele is associated with reduced expression in brain nucleus accumbens (basal ganglia) GTEx Portal

Lifestyle considerations

No lifestyle considerations on file for this variant.

Frequently asked questions

What does the ADAMTSL3 gene do?

ADAMTSL3 encodes a protein that is part of the extracellular matrix, the structural scaffolding surrounding cells. Research has classified it among extracellular matrix genes and found variants near it to be associated with adult height, suggesting a role in growth and developmental processes.

Is rs10906982 associated with height?

Yes, two independent genome-wide association studies have found evidence linking this locus to adult height. The stronger study reached genome-wide significance (P < 5 x 10^-7) in a sample of over 30,000 European-ancestry individuals.

How much of height variation does rs10906982 explain?

The individual contribution of this variant is small. When combined with 19 other identified height variants, all 20 together explain approximately 3% of height variation across large populations; the vast majority of height differences stem from other genetic and environmental factors.

Has rs10906982 been studied in non-European populations?

The primary height associations at this locus have been reported in European-ancestry cohorts. A large multi-ethnic genome-wide study (the PAGE consortium, n=49,839 non-European participants) highlighted that genetic effect sizes and allele frequencies can differ across ancestries, but did not specifically report on this locus.

What do the GTEx expression results show for this variant?

GTEx eQTL data show the alternative allele at rs10906982 is linked to reduced expression of UBE2Q2P1 in seven tissues including adipose, lung, and nerve tissue, and to reduced expression of a second nearby gene in brain nucleus accumbens. These are molecular signals describing gene regulation patterns; eQTL findings do not directly translate to clinical outcomes.