CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, China.
CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, China.
PLoS Genet. 2023 Jul 17;19(7):e1010786. doi: 10.1371/journal.pgen.1010786. eCollection 2023 Jul.
Human ear morphology, a complex anatomical structure represented by a multidimensional set of correlated and heritable phenotypes, has a poorly understood genetic architecture. In this study, we quantitatively assessed 136 ear morphology traits using deep learning analysis of digital face images in 14,921 individuals from five different cohorts in Europe, Asia, and Latin America. Through GWAS meta-analysis and C-GWASs, a recently introduced method to effectively combine GWASs of many traits, we identified 16 genetic loci involved in various ear phenotypes, eight of which have not been previously associated with human ear features. Our findings suggest that ear morphology shares genetic determinants with other surface ectoderm-derived traits such as facial variation, mono eyebrow, and male pattern baldness. Our results enhance the genetic understanding of human ear morphology and shed light on the shared genetic contributors of different surface ectoderm-derived phenotypes. Additionally, gene editing experiments in mice have demonstrated that knocking out the newly ear-associated gene (Intu) and a previously ear-associated gene (Tbx15) causes deviating mouse ear morphology.
人类耳朵形态是一种复杂的解剖结构，由多维相关且可遗传的表型组成，其遗传结构尚不清楚。在这项研究中，我们使用深度学习分析了来自欧洲、亚洲和拉丁美洲五个不同队列的 14921 个人的数字面部图像，对 136 种耳朵形态特征进行了定量评估。通过 GWAS 荟萃分析和 C-GWAS（一种最近引入的有效结合多个性状 GWAS 的方法），我们确定了 16 个与各种耳朵表型相关的遗传位点，其中 8 个先前与人类耳朵特征无关。我们的研究结果表明，耳朵形态与其他由外胚层衍生的特征（如面部变异、单眉和男性型秃发）共享遗传决定因素。我们的研究结果提高了对人类耳朵形态遗传理解，并揭示了不同由外胚层衍生的表型的共享遗传贡献者。此外，对小鼠的基因编辑实验表明，敲除新的与耳朵相关的基因(Intu)和先前与耳朵相关的基因(Tbx15)会导致小鼠耳朵形态的偏离。
