Identification of five novel genetic loci related to facial morphology by genome-wide association studies

Seongwon Cha, Ji Eun Lim, Ah Yeon Park, Jun Hyeong Do, Si Woo Lee, Chol Shin, Nam Han Cho, Ji One Kang, Jeong Min Nam, Jong Sik Kim, Kwang Man Woo, Seung Hwan Lee, Jong Yeol Kim, Bermseok Oh

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)


Background: Face morphology is strongly determined by genetic factors. However, only a small number of genes related to face morphology have been identified to date. Here, we performed a two-stage genome-wide association study (GWAS) of 85 face morphological traits in 7569 Koreans (5643 in the discovery set and 1926 in the replication set). Results: In this study, we analyzed 85 facial traits, including facial angles. After discovery GWAS, 128 single nucleotide polymorphisms (SNPs) showing an association of P < 5 × 10- 6 were selected to determine the replication of the associations, and meta-analysis of discovery GWAS and the replication analysis resulted in five genome-wide significant loci. The OSR1-WDR35 [rs7567283, G allele, beta (se) = -0.536 (0.096), P = 2.75 × 10- 8] locus was associated with the facial frontal contour; the HOXD1-MTX2 [rs970797, A allele, beta (se) = 0.015 (0.003), P = 3.97 × 10- 9] and WDR27 [rs3736712, C allele, beta (se) = 0.293 (0.048), P = 8.44 × 10- 10] loci were associated with eye shape; and the SOX9 [rs2193054, C allele, beta (se) (ln-transformed) = -0.007 (0.001), P = 6.17 × 10- 17] and DHX35 [rs2206437, A allele, beta (se) = -0.283 (0.047), P = 1.61 × 10- 9] loci were associated with nose shape. WDR35 and SOX9 were related to known craniofacial malformations, i.e., cranioectodermal dysplasia 2 and campomelic dysplasia, respectively. In addition, we found three independent association signals in the SOX9 locus, and six known loci for nose size and shape were replicated in this study population. Interestingly, four SNPs within these five face morphology-related loci showed discrepancies in allele frequencies among ethnic groups. Conclusions: We identified five novel face morphology loci that were associated with facial frontal contour, nose shape, and eye shape. Our findings provide useful genetic information for the determination of face morphology.

Original languageEnglish
Article number481
JournalBMC Genomics
Issue number1
Publication statusPublished - 2018 Jun 19


  • DHX35
  • Face morphology
  • GWAS
  • HOXD1-MTX2
  • Korean
  • OSR1-WDR35
  • SOX9
  • WDR27

ASJC Scopus subject areas

  • Biotechnology
  • Genetics


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