A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation.
A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation.
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DOI：
10.1038/ncomms11616
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发表时间：
2016-05-19
影响因子：
16.6
通讯作者：
Ruiz-Linares A
中科院分区：
文献类型：
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作者：
Adhikari K;Fuentes-Guajardo M;Quinto-Sánchez M;Mendoza-Revilla J;Camilo Chacón-Duque J;Acuña-Alonzo V;Jaramillo C;Arias W;Lozano RB;Pérez GM;Gómez-Valdés J;Villamil-Ramírez H;Hunemeier T;Ramallo V;Silva de Cerqueira CC;Hurtado M;Villegas V;Granja V;Gallo C;Poletti G;Schuler-Faccini L;Salzano FM;Bortolini MC;Canizales-Quinteros S;Cheeseman M;Rosique J;Bedoya G;Rothhammer F;Headon D;González-José R;Balding D;Ruiz-Linares A
我们报告了一个全基因组关联扫描的面部特征在16000拉丁美洲人。我们对14个性状进行了有序量表评估，发现4个基因组区域的单核苷酸多态性（SNP）与3个鼻相关性状显著相关（P值<5 × 10−8）：鼻小柱倾斜度（4 q31），鼻梁宽度（6p 21）和鼻翼宽度（7 p13和20 p11）。在一个3,000人的子样本中，我们获得了与9个序数表型相关的数量性状，以及鼻根位置的测量。定量分析证实了基于顺序的关联，确定了2 q12中与下巴突出相关的SNP，并复制了PAX 3中鼻根位置与SNP的相关性。EDAR、DCHS 2、RUNX 2和GLI 3基因的SNPs分别在2 q12、4 q31、6p 21和7 p13中观察到最强的关联。20 p11中的相关SNP延伸至PAX 1。与EDAR对颏前突的作用一致，我们记录了具有改良的Edar功能的小鼠下颌骨长度的改变。 人类在面部外观上表现出很大的多样性，这种变化是高度遗传的。在这里，Andres Ruiz-Linares及其同事研究了混合拉丁美洲人的面部特征，并确定了14种面部特征的全基因组关联，包括影响鼻子形态的四个基因位点（RUNX 2，GLI 3，DCHS 2和PAX 1）。
We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values<5 × 10−8) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar funtion. Humans show great diversity in facial appearance and this variation is highly heritable. Here, Andres Ruiz-Linares and colleagues examined facial features in admixed Latin Americans and identify genome-wide associations for 14 facial traits, including four gene loci (RUNX2, GLI3, DCHS2 and PAX1) influencing nose morphology.