PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humans.

ABSTRACT: Dental morphology varies greatly throughout evolution, including in the human lineage, but little is known about the biology of this variation. Here, we use multiomics analyses to examine the genetics of variation in tooth crown dimensions. In a human cohort with mixed continental ancestry, we detected genome-wide significant associations at 18 genome regions. One region includes EDAR, a gene known to impact dental features in East Asians. Furthermore, we find that EDAR variants increase the mesiodistal diameter of all teeth, following an anterior-posterior gradient of decreasing strength. Among the 17 novel-associated regions, we replicate 7/13 in an independent human cohort and find that 4/12 orthologous regions affect molar size in mice. Two association signals point to compelling candi

SUBMITTER: Li Q 

PROVIDER: S-EPMC11789201 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature