Genetic determination of human facial morphology: links between cleft-lips and normal variation

S Boehringer, Fedde Lijn, Fan Liu, M Gunther, S Sinigerova, S Nowak, KU Ludwig, R Herberz, Stefan Klein, Bert Hofman, André Uitterlinden, Wiro Niessen, Monique Breteler, Aad van der Lugt, RP Wurtz, MM Nothen, B Horsthemke, D Wieczorek, E Mangold, Manfred Kayser

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83 Citations (Scopus)

Abstract

Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with non-syndromic cleft lip with or without cleft palate (NSCL/P), and other previous studies showed distinctly differing facial distance measurements when comparing unaffected relatives of NSCL/P patients with normal controls. Here, we test the hypothesis that genetic loci involved in NSCL/P also influence normal variation in facial morphology. We tested 11 SNPs from 10 genomic regions previously showing replicated evidence of association with NSCL/P for association with normal variation of nose width and bizygomatic distance in two cohorts from Germany (N=529) and the Netherlands (N=2497). The two most significant associations found were between nose width and SNP rs1258763 near the GREM1 gene in the German cohort (P=6 x 10(-4)), and between bizygomatic distance and SNP rs987525 at 8q24.21 near the CCDC26 gene (P-0.017) in the Dutch sample. A genetic prediction model explained 2% of phenotype variation in nose width in the German and 0.5% of bizygomatic distance variation in the Dutch cohort. Although preliminary, our data provide a first link between genetic loci involved in a pathological facial trait such as NSCL/P and variation of normal facial morphology. Moreover, we present a first approach for understanding the genetic basis of human facial appearance, a highly intriguing trait with implications on clinical practice, clinical genetics, forensic intelligence, social interactions and personal identity. European Journal of Human Genetics (2011) 19, 1192-1197; doi:10.1038/ejhg.2011.110; published online 22 June 2011
Original languageUndefined/Unknown
Pages (from-to)1192-1197
Number of pages6
JournalEuropean Journal of Human Genetics
Volume19
Issue number11
DOIs
Publication statusPublished - 2011

Research programs

  • EMC MGC-02-26-01
  • EMC MM-01-25-01
  • EMC MM-01-39-09-A
  • EMC NIHES-01-64-01
  • EMC NIHES-03-30-01
  • EMC NIHES-03-30-03

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