Genome-wide mapping of global-to-local genetic effects on human facial shape

Nat Genet. 2018 Mar;50(3):414-423. doi: 10.1038/s41588-018-0057-4. Epub 2018 Feb 19.

Abstract

Genome-wide association scans of complex multipartite traits like the human face typically use preselected phenotypic measures. Here we report a data-driven approach to phenotyping facial shape at multiple levels of organization, allowing for an open-ended description of facial variation while preserving statistical power. In a sample of 2,329 persons of European ancestry, we identified 38 loci, 15 of which replicated in an independent European sample (n = 1,719). Four loci were completely new. For the others, additional support (n = 9) or pleiotropic effects (n = 2) were found in the literature, but the results reported here were further refined. All 15 replicated loci highlighted distinctive patterns of global-to-local genetic effects on facial shape and showed enrichment for active chromatin elements in human cranial neural crest cells, suggesting an early developmental origin of the facial variation captured. These results have implications for studies of facial genetics and other complex morphological traits.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chromosome Mapping*
  • Cohort Studies
  • Face / anatomy & histology*
  • Genetic Association Studies
  • Genome-Wide Association Study*
  • Genotype
  • Humans
  • Maxillofacial Development / genetics
  • Multifactorial Inheritance / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • United States
  • White People / genetics
  • Young Adult