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Non-syndromic Cleft Lip and Palate Polymorphisms Affect Normal Lip Morphology.

Caryl Wilson-Nagrani1, Stephen Richmond1, Lavinia Paternoster2

  • 1Department of Orthodontics, University Dental Hospital, Cardiff, United Kingdom.

Frontiers in Genetics
|November 9, 2018
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Summary

Genetic variants linked to non-syndromic cleft lip (NSCL/P) influence normal lip shapes, like a narrow philtrum. However, these genetic risk scores are unlikely to predict NSCL/P risk effectively.

Keywords:
ALSPACNOGcleftcraniofacialfaciallip morphologypalateskeletal pattern

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Area of Science:

  • Genetics
  • Human Morphology
  • Facial Development

Background:

  • Non-syndromic cleft lip with or without palate (NSCL/P) is a common facial malformation.
  • Genome-wide association studies (GWAS) have identified 19 genetic loci associated with NSCL/P in European populations.
  • Previous research on facial morphology has limitations in detailed lip landmark analysis.

Purpose of the Study:

  • To investigate associations between 19 known NSCL/P single nucleotide polymorphisms (SNPs) and normal lip phenotypes.
  • To determine if genetic variants influencing NSCL/P also affect subtle lip morphology in the general population.
  • To assess the potential of a polygenic risk score (PRS) for NSCL/P SNPs as a predictor of lip shape.

Main Methods:

  • Utilized 3D laser-scanned facial images from 4,747 subjects in the Avon Longitudinal Study of Parents and Children (ALSPAC).
  • Analyzed genetic data from 3,643 ALSPAC participants.
  • Applied a detailed categorical scale to assess normal lip phenotypes and calculated a PRS from 19 NSCL/P SNPs.

Main Results:

  • A PRS combining 19 NSCL/P SNPs was significantly associated with a V-shaped Cupid's bow (P = 3 × 10⁻⁴) and narrow philtrum (P = 2 × 10⁻⁴).
  • The SNP rs227731 showed strong evidence of association with a skeletal II pattern (P = 5 × 10⁻⁶).
  • These findings indicate that common NSCL/P SNPs impact lip morphology in the general population.

Conclusions:

  • Known NSCL/P-associated SNPs influence lip phenotypes in individuals without clefts.
  • An elevated PRS for NSCL/P is linked to specific lip shapes, including a narrow philtrum and V-shaped Cupid's bow.
  • The observed differences in PRS are likely too small to serve as a reliable clinical marker for NSCL/P risk.