TY - JOUR
T1 - Identification of five novel genetic loci related to facial morphology by genome-wide association studies
AU - Cha, Seongwon
AU - Lim, Ji Eun
AU - Park, Ah Yeon
AU - Do, Jun Hyeong
AU - Lee, Si Woo
AU - Shin, Chol
AU - Cho, Nam Han
AU - Kang, Ji One
AU - Nam, Jeong Min
AU - Kim, Jong Sik
AU - Woo, Kwang Man
AU - Lee, Seung Hwan
AU - Kim, Jong Yeol
AU - Oh, Bermseok
N1 - Publisher Copyright:
© 2018 The Author(s).
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/6/19
Y1 - 2018/6/19
N2 - 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.
AB - 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.
KW - DHX35
KW - Face morphology
KW - GWAS
KW - HOXD1-MTX2
KW - Korean
KW - OSR1-WDR35
KW - SOX9
KW - WDR27
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UR - http://www.scopus.com/inward/citedby.url?scp=85048958841&partnerID=8YFLogxK
U2 - 10.1186/s12864-018-4865-9
DO - 10.1186/s12864-018-4865-9
M3 - Article
C2 - 29921221
AN - SCOPUS:85048958841
VL - 19
JO - BMC Genomics
JF - BMC Genomics
SN - 1471-2164
IS - 1
M1 - 481
ER -