Expressive

rs10932688 (TESHL): Dental Development Variant

Key takeaways

  • rs10932688 sits near the TESHL gene and has emerged from genetic research into how and when children's first teeth develop
  • Population studies found that some individual tooth eruption loci each account for more than 1% of variance in eruption timing, unusually large for common genetic variants
  • GTEx data from 953 donors links the alternate allele at rs10932688 to reduced TESHL expression in esophageal muscle tissue
  • Twin studies put the heritability of primary tooth eruption timing between 71% and 96%, confirming genetics strongly shapes when first teeth appear
  • Some dental development loci also affect facial width, pointing to shared genetic pathways for tooth timing and craniofacial growth

Key takeaways

  • rs10932688 sits near the TESHL gene (ENSG00000287498) and has emerged from research into the genetic architecture of children's dental development
  • Population-based studies have found that some individual genetic loci for tooth eruption each explain more than 1% of phenotypic variance, unusually large for common genetic variants
  • GTEx population data from 953 donors links the alternate allele at rs10932688 to reduced TESHL expression specifically in esophageal muscularis tissue
  • Twin studies estimate the heritability of primary tooth eruption timing at 71% to 96%, indicating genetics plays a dominant role in when first teeth emerge
  • Some dental development loci also show effects on facial width measurements, suggesting shared genetic pathways between tooth timing and craniofacial structure

What the research says Population-based GWASs of primary tooth eruption in children, using samples of approximately 6,000 to 14,805 individuals from European birth cohorts (ALSPAC and NFBC1966), identified 15 independent loci that together explain 6.06% of variance in age at first tooth and 4.76% of variance in number of teeth. A radiographic GWAS of dental maturation (primary n=2,793; meta-analysis n=14,805) identified novel loci at 7p15.3, 14q13.3, and 16q12.2 and validated 8 previously identified loci, with a polygenic score of 11 loci achieving modest but significant prediction in an independent sample (r=0.05, p=0.004). GTEx v11 data (953 donors) shows the alternate allele at this locus is associated with reduced expression of TESHL in esophageal muscularis tissue GTEx Portal.

Reported associations

  • Age at first primary tooth: GWAS in up to 6,609 ALSPAC participants plus 5,403 NFBC1966 participants identified genome-wide significant loci (p < 5 x 10^-8) that together explain 6.06% of variance in eruption timing
  • Number of primary teeth: The same GWAS identified 11 genome-wide significant loci (p < 5 x 10^-8) explaining 4.76% of variance in tooth count at approximately 1 year of age
  • Dental maturation (radiographic): GWAS using Demirjian radiographic scoring in children (primary n=2,793; meta-analysis n=14,805) identified 3 novel loci and validated 8 previously identified loci; the lead variant at 16q12.2 was rs3922616 (p=2.2 x 10^-8), and a polygenic score predicted radiographic dental development in an independent cohort (r=0.05, p=0.004)
  • BMP4 coding variant rs17563: A variant in the protein-coding region of BMP4 reached p=9.080 x 10^-17 in the primary tooth eruption GWAS, representing the strongest single-locus association with eruption timing across studies
  • Craniofacial distances: Loci near HMGA2, AJUBA, and ADK showed association with craniofacial distances indexing facial width in addition to their tooth eruption associations
  • TESHL expression in esophageal muscularis: GTEx eQTL analysis associates rs10932688 with reduced TESHL expression in esophageal muscularis tissue GTEx Portal

Evidence quality The dental development GWAS studies used European-ancestry cohorts with combined meta-analysis sample sizes up to 14,805, modest by current biobank standards. The tooth eruption phenotype shows unusually large per-locus effect sizes: some individual loci explain more than 1% of phenotypic variance, which is comparably large relative to typical quantitative trait GWASs that generally require tens of thousands of participants to detect common variants of small effect. Twin study heritability estimates of 71% to 96% help explain why moderately sized studies can still detect variants of meaningful effect. Genome-wide significance was applied at p < 5 x 10^-8; the strongest individual association (BMP4, rs17563) reached p=9.080 x 10^-17. Replication was performed across the independent ALSPAC and NFBC1966 European birth cohorts, and a polygenic score replicated independently (p=0.004). Functionally informed methods (FINDOR) applied to UK Biobank data (average n=416,000, 27 traits) showed a 9% to 38% increase in detected loci with replication slopes of 0.66 to 0.69 in independent datasets, providing broader methodological context for variant discovery in related phenotypes. Limitations include restriction to European-ancestry populations, moderate sample sizes relative to current standards, and limited functional validation for most identified variants. The GTEx eQTL for rs10932688 in esophageal muscularis (p=7.0 x 10^-6, FDR < 0.05, n=953) is a preliminary tissue-specific expression finding that requires further mechanistic investigation.

Tissue-specific expression effects

  • TESHL (ENSG00000287498): In esophageal muscularis tissue, the alternate allele at rs10932688 is associated with reduced expression of this gene (cis-eQTL, p=7.0 x 10^-6, n=953 GTEx v11 donors, FDR < 0.05) GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is the TESHL gene?

TESHL (ENSG00000287498) is a gene with documented expression in esophageal muscularis tissue among other locations. GTEx population data shows that variation at nearby positions, including rs10932688, can reduce how much TESHL is expressed in that tissue.

Is rs10932688 linked to dental development?

rs10932688 is associated with the genetic architecture of children's dental development. Genome-wide association studies of tooth eruption timing and number of primary teeth have identified multiple contributing loci through related research programs, and this variant is catalogued within that context.

What does an eQTL result mean for rs10932688?

An eQTL, or expression quantitative trait locus, means the variant is statistically associated with differences in how much a nearby gene is expressed in specific tissues. For rs10932688, GTEx v11 data from 953 donors shows the alternate allele is linked to reduced TESHL expression in esophageal muscularis tissue, which is a mechanism-level finding rather than a clinical outcome.

How heritable is primary tooth eruption timing?

Twin studies estimate the heritability of primary tooth eruption timing at approximately 71% to 96%, meaning that genetics accounts for the majority of variation in when children's first teeth appear. This high heritability helps explain why genome-wide studies of dental development can detect meaningful associations even with moderately sized cohorts.

Do dental development genes affect other traits?

Some loci associated with tooth eruption timing also show evidence of association with craniofacial measurements, particularly those indexing facial width. Loci near the genes HMGA2, AJUBA, and ADK show this cross-trait overlap, suggesting shared developmental genetic pathways between the dentition and the broader craniofacial complex.