Genomewide Association Study of African Children Identifies Association of SCHIP1 and PDE8A with Facial Size and Shape.
Genomewide Association Study of African Children Identifies Association of SCHIP1 and PDE8A with Facial Size and Shape.
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DOI：
10.1371/journal.pgen.1006174
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发表时间：
2016-08
期刊：
影响因子：
4.5
通讯作者：
Spritz RA
中科院分区：
文献类型：
--
作者：
Cole JB;Manyama M;Kimwaga E;Mathayo J;Larson JR;Liberton DK;Lukowiak K;Ferrara TM;Riccardi SL;Li M;Mio W;Prochazkova M;Williams T;Li H;Jones KL;Klein OD;Santorico SA;Hallgrimsson B;Spritz RA
人脸是一个复杂的集合体，它由多种多样但明显可遗传的解剖结构组成，这些结构使我们每个人都是独特的、可区分的和可识别的。相对而言，我们对正常人类面部变异的遗传基础知之甚少。为了解决这个问题，我们进行了一个大的全基因组关联研究和两个独立的复制研究班图非洲儿童和青少年从姆万扎，坦桑尼亚，一个地区，是遗传和环境相对同质。我们测试了来自3D成像和标准面部形态测量点的自动标记的面部形状和大小表型的遗传关联。基因SCHIP 1和PDE 8A内的SNP与GWAS和复制队列中的面部大小测量相关，并通过了严格的全基因组显著性阈值，该阈值针对34个相关性状的多重测试进行了调整。对于SCHIP 1和PDE 8A，我们通过整体原位杂交和RNA-seq证明了它们在发育中的小鼠面部中的明确表达，支持它们参与面部形态发生。另外10个位点表现出与面部形状的各种措施的暗示性关联。我们的研究结果与以前对欧洲白人的研究不同，增加了对正常面部发育遗传基础的理解，并提供了与人类疾病和法医学相关的见解。人脸是由不同但相关的解剖结构组成的，这些结构共同使个人和家庭都可以识别。很明显，人类的面部有很强的遗传成分，虽然面部的遗传学已经研究了好几年，但已知影响正常人类面部发育和面部形状的基因相对较少。我们在这里报告了一项大规模的人类遗传学研究，在这项研究中，我们成功地识别和复制了与非洲儿童使用先进的3D面部成像正常面部变异相关的遗传标记。我们确定了两个与人类面部大小相关的重要复制基因，SCHIP 1和PDE 8A，证明了它们在小鼠面部发育中的明确表达，并确定了10个额外的人类面部形状的候选遗传位点。人类面部发育的基因发现是诊断和治疗颅面综合征以及发展人类面部法医建模的重要第一步。
The human face is a complex assemblage of highly variable yet clearly heritable anatomic structures that together make each of us unique, distinguishable, and recognizable. Relatively little is known about the genetic underpinnings of normal human facial variation. To address this, we carried out a large genomewide association study and two independent replication studies of Bantu African children and adolescents from Mwanza, Tanzania, a region that is both genetically and environmentally relatively homogeneous. We tested for genetic association of facial shape and size phenotypes derived from 3D imaging and automated landmarking of standard facial morphometric points. SNPs within genes SCHIP1 and PDE8A were associated with measures of facial size in both the GWAS and replication cohorts and passed a stringent genomewide significance threshold adjusted for multiple testing of 34 correlated traits. For both SCHIP1 and PDE8A, we demonstrated clear expression in the developing mouse face by both whole-mount in situ hybridization and RNA-seq, supporting their involvement in facial morphogenesis. Ten additional loci demonstrated suggestive association with various measures of facial shape. Our findings, which differ from those in previous studies of European-derived whites, augment understanding of the genetic basis of normal facial development, and provide insights relevant to both human disease and forensics. The human face is made up of distinct yet related anatomic structures that together make both individuals and families recognizable. It is clear there is a strong genetic component to the human face, and though the genetics of the face have been studied for several years, there are relatively few genes known to impact normal human facial development and facial shape. We report here a large-scale human genetic study in which we successfully identify and replicate genetic markers associated with normal facial variation using advanced 3D facial imaging in African children. We identified two significant replicated genes associated with measures of human facial size, SCHIP1 and PDE8A, demonstrated their clear expression in the developing face in the mouse, and identified 10 additional candidate genetic loci for human facial shape. Gene discovery for human facial development is an important first step for both diagnosing and treating craniofacial syndromes and for developing forensic modeling of the human face.