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 x 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 x 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 x 10− 9] and WDR27 [rs3736712, C allele, beta (se) = 0.293 (0.048), P = 8.44 x 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 x 10− 17] and DHX35 [rs2206437, A allele, beta (se) = −0.283 (0.047), P = 1.61 x 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.
저자: 차성원(한국한의학연구원),임지은(경희대학교 의과대학),오범석(경희대학교 의과대학),박아연(한국한의학연구원),도준형(한국한의학연구원),이시우(한국한의학연구원),신철(고려대학교 의과대학),조남한(아주대학교 의과대학),강지원(경희대학교 의과대학),남정민(경희대학교 의과대학),김종식(검찰청),우광만(검찰청),이승환(검찰청),김종열(한국한의학연구원) |
