Insights into the genetic architecture of the human face

Nat Genet. 2021 Jan;53(1):45-53. doi: 10.1038/s41588-020-00741-7. Epub 2020 Dec 7.

Abstract

The human face is complex and multipartite, and characterization of its genetic architecture remains challenging. Using a multivariate genome-wide association study meta-analysis of 8,246 European individuals, we identified 203 genome-wide-significant signals (120 also study-wide significant) associated with normal-range facial variation. Follow-up analyses indicate that the regions surrounding these signals are enriched for enhancer activity in cranial neural crest cells and craniofacial tissues, several regions harbor multiple signals with associations to different facial phenotypes, and there is evidence for potential coordinated actions of variants. In summary, our analyses provide insights into the understanding of how complex morphological traits are shaped by both individual and coordinated genetic actions.

Publication types

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

MeSH terms

  • Acetylation
  • Enhancer Elements, Genetic / genetics
  • Epistasis, Genetic
  • Extremities / embryology
  • Face / anatomy & histology*
  • Face / embryology
  • Genetic Loci
  • Genome-Wide Association Study*
  • Histones / metabolism
  • Humans
  • Lysine / metabolism
  • Meta-Analysis as Topic
  • Multivariate Analysis
  • Neural Crest / cytology
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Skull / embryology
  • United Kingdom
  • United States

Substances

  • Histones
  • Lysine