Department of Electrical Engineering, ESAT/PSI, KU Leuven, Leuven, Belgium.
Medical Imaging Research Center, MIRC, UZ Leuven, Leuven, Belgium.
Nat Genet. 2018 Mar;50(3):414-423. doi: 10.1038/s41588-018-0057-4. Epub 2018 Feb 19.
Genome-wide association scans of complex multipartite traits like the human face typically use preselected phenotypic measures. Here we report a data-driven approach to phenotyping facial shape at multiple levels of organization, allowing for an open-ended description of facial variation while preserving statistical power. In a sample of 2,329 persons of European ancestry, we identified 38 loci, 15 of which replicated in an independent European sample (n = 1,719). Four loci were completely new. For the others, additional support (n = 9) or pleiotropic effects (n = 2) were found in the literature, but the results reported here were further refined. All 15 replicated loci highlighted distinctive patterns of global-to-local genetic effects on facial shape and showed enrichment for active chromatin elements in human cranial neural crest cells, suggesting an early developmental origin of the facial variation captured. These results have implications for studies of facial genetics and other complex morphological traits.
全基因组关联扫描复杂的多部分特征，如人脸，通常使用预先选择的表型测量。在这里，我们报告了一种数据驱动的方法来对多个组织层次的面部形状进行表型分析，允许对面部变异进行开放式描述，同时保持统计能力。在一个由 2329 名欧洲血统的个体组成的样本中，我们确定了 38 个位点，其中 15 个在一个独立的欧洲样本中得到了复制（n=1719）。其中 4 个是全新的。对于其他的，在文献中发现了额外的支持（n=9）或多效性效应（n=2），但这里报告的结果进一步得到了细化。所有复制的 15 个位点突出了全球到局部遗传效应对面部形状的独特影响模式，并显示了人类颅神经嵴细胞中活性染色质元件的富集，表明所捕获的面部变异具有早期发育起源。这些结果对面部遗传学和其他复杂形态特征的研究具有重要意义。
