外异蛋白受体基因(ectodysplasin A receptor,EDAR)是调控外胚层发育的重要基因。其关键错义突变EDARV370A的衍生等位基因370A在东亚和美洲原住民中具有很高的频率,但在非洲和欧洲罕见,该突变造成这些人群许多外胚层发育衍生表型的差异,包括东亚人特有的较直且厚的头发、较多的外泌汗腺、女性较小的乳房及铲形门齿等。目前,EDARV370A与同为外胚层衍生表型的人类头面部及耳部形态特征的关联尚不十分明确。本研究在715例新疆维吾尔族亚欧混合人群中,进行了EDARV370A与一系列系统的面部形态特征及耳朵形态表型的关联分析,以期更全面系统地理解EDARV370A对面部和耳朵形态的影响。研究表型包括利用本课题组近期发表的对三维面部照片自动化面部地标点标记方法获得的136个面部定量表型、1个下巴类型的定序分类表型以及6个耳朵形态的定序分类表型。研究发现EDARV370A与8个面部形态的定量表型、下巴类型以及3个耳朵形态定序分类表型显著相关(多重检验校正后P<0.05)。本研究结果进一步明确了EDARV370A的遗传多效性及其在亚欧混合人群中对面部和耳朵形态的影响。

The ectodysplasinA receptor gene (EDAR) plays an important role in the development of ectoderm. The derived G allele of its key missense variant EDARV370A is prevalent in East Asians and Americans, but rare in Africans and Europeans. This leads to distinct ectodermal-derived phenotypes between different continental groups, such as the straighter and thicker hair, more eccrine sweat glands, feminine smaller breasts, shovel incisors characteristic of East Asians. At present, we know little about the association between EDARV370A and facial and ear morphology characteristics. To better understand the effect of EDARV370A on craniofacial phenotypes, we systematically examined the association between EDARV370A and 136 facial quantitative phenotypes, one chin ordinal phenotype and six ear ordinal phenotypes in 715 Uyghurs. The quantitative phenotypes were derived by applying our automated landmark annotation method to facial 3D photos and the ordinal phenotypes were manually graded from facial 2D photos. The analysis identified significant association (P<0.05 after multiple testing correction) between EDARV370A and eight facial phenotypes, one chin phenotype and three ear morphology phenotypes. Our study thus elucidated the pleotropic effect of EDARV370A on craniofacial phenotypes in a European-Asian admixed Uyghur population.