Syndrome-informed phenotyping identifies a polygenic background for achondroplasia-like facial variation in the general population.

ABSTRACT: Human craniofacial shape is highly variable yet highly heritable with numerous genetic variants interacting through multiple layers of development. Here, we hypothesize that Mendelian phenotypes represent the extremes of a phenotypic spectrum and, using achondroplasia as an example, we introduce a syndrome-informed phenotyping approach to identify genomic loci associated with achondroplasia-like facial variation in the general population. We compare three-dimensional facial scans from 43 individuals with achondroplasia and 8246 controls to calculate achondroplasia-like facial scores. Multivariate GWAS of the control scores reveals a polygenic basis for facial variation along an achondroplasia-specific shape axis, identifying genes primarily involved in skeletal development. Jointly modelin

SUBMITTER: Vanneste M 

PROVIDER: S-EPMC11612227 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature