Abstract
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.
| Original language | English |
|---|---|
| Article number | e1010786 |
| Journal | PLoS Genetics |
| Volume | 19 |
| Issue number | 7 July |
| DOIs | |
| Publication status | Published - 17 Jul 2023 |
Bibliographical note
Funding Information:Specified authors were supported by research grants as follows: Strategic Priority Research Program of Chinese Academy of Sciences, XDB38010400 (FL), XDB38020400 (SW), and XDC01000000 (FL); Shanghai Municipal Science and Technology Major Project (2017SHZDZX01 to FL, SW, and LJ); the National Natural Science Foundation of China (NSFC) 81930056 (FL), 31521003 (SW), and 31900408 (MZ); Science and Technology Service Network Initiative of Chinese Academy of Sciences KFJ-STS-ZDTP-079 (FL); the Beijing Advanced Discipline Fund (FL); CAS Interdisciplinary Innovation Team Project (SW); Shanghai Science and Technology Commission Excellent Academic Leaders Program 22XD1424700 (SW); the CAS Project for Young Scientists in Basic Research YSBR-077 (SW); National Science & Technology Basic Research Project 2015FY111700 (LJ); the 111 Project B13016 (LJ); China Postdoctoral Science Foundation 2019M651352 (MZ); Leverhulme Trust grant F/07 134/DF (A.R.-L.); Biotechnology and Biological Sciences Research Council grant BB/I021213/1 (A.R.-L.). The Rotterdam Study is supported by the Erasmus MC and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research (NWO); the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE) the Netherlands Genomics Initiative (NGI); the Ministry of Education, Culture and Science; the Ministry of Health Welfare and Sport; the European Commission (DG XII); and the Municipality of Rotterdam. The generation and management of GWAS genotype data for the Rotterdam Study were executed by the Human Genotyping Facility of the Genetic Laboratory for Population Genomics of the Department of Internal Medicine, Erasmus MC. TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. P.G.H acknowledges the use of funding from the BrightFocus Foundation. The generation and management of GWAS genotype data for the TZL and NSPT was collected and executed by the collaboration of CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China and the State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank all sample donors for their contribution to this project. We would like to express our gratitude to Winston Rojas-Montoya for his invaluable support at the Universidad de Antioquia during the difficult period following the unfortunate passing of Gabriel Bedoya.
Publisher Copyright:
© 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
