Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci

doi:10.1371/journal.pgen.1010786

	Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci
	Li, Yi 1,2; Xiong, Ziyi 3,4; Zhang, Manfei 1,5,6; Hysi, Pirro G.7; Qian, Yu 2,8; Adhikari, Kaustubh 9,10,11; Weng, Jun 12,13; Wu, Sijie 1,6,14; Du, Siyuan 1,5,15; Gonzalez-Jose, Rolando 16; Schuler-Faccini, Lavinia 17; Bortolini, Maria-Catira 17; Acuna-Alonzo, Victor 18; Canizales-Quinteros, Samuel 19; Gallo, Carla 20; Poletti, Giovanni 20; Bedoya, Gabriel 21; Rothhammer, Francisco 22; Wang, Jiucun 6,14; Tan, Jingze 14; Yuan, Ziyu 23; Jin, Li 1,6,14,23; Uitterlinden, Andre G.4,24; Ghanbari, Mohsen 4; Ikram, M. Arfan 4; Nijsten, Tamar 25; Zhu, Xiangyu D.12,13,26; Lei, Zhen12,13,26 ; Jia, Peilin 2; Ruiz-Linares, Andres 9,10,14,27; Spector, Timothy D.7; Wang, Sijia 1,28; Kayser, Manfred 3; Liu, Fan 2,3
发表期刊	PLOS GENETICS
ISSN	1553-7404
	2023-07-01
卷号	19 期号:7 页码:25
通讯作者	Wang, Sijia(wangsijia@picb.ac.cn) ; Liu, Fan(f.liu@erasmusmc.nl)
摘要	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. Author summaryHuman ear morphology varies widely, with largely inherited differences. However, the genetic basis for these differences is not well understood. To better understand the genetics of human ear morphology, we analyzed 136 ear traits from digital facial images of 14,921 individuals from three continents using GWAS meta-analysis and the recently developed C-GWAS method. We identified 16 genetic loci associated with ear morphology, eight of which had not been previously associated with ear features. These genetic loci can serve as candidates for future research to understand the function of these genes. Additionally, we have demonstrated the impact of two ear-associated loci on ear morphology in gene-edited mice. This study provides new insights into the complex genetics of the human ear.
DOI	10.1371/journal.pgen.1010786
关键词[WOS]	EXPRESSION ; IDENTIFICATION ; EDAR ; ANNOTATION ; EVOLUTION ; EDARV370A ; DATABASE ; VARIANT ; ATLAS ; HAIR
收录类别	SCI
语种	英语
资助项目	Chinese Academy of Sciences[B13016] ; Chinese Academy of Sciences[2019M651352] ; Chinese Academy of Sciences[F/07 134/DF] ; Shanghai Municipal Science and Technology Major Project[BB/I021213/1] ; National Natural Science Foundation of China (NSFC) ; Science and Technology Service Network Initiative of Chinese Academy of Sciences ; Beijing Advanced Discipline Fund ; CAS Interdisciplinary Innovation Team Project ; Shanghai Science and Technology Commission Excellent Academic Leaders Program ; CAS Project for Young Scientists in Basic Research ; National Science amp; Technology Basic Research Project ; 111 Project ; China Postdoctoral Science Foundation ; Leverhulme Trust ; Biotechnology and Biological Sciences Research Council ; Erasmus MC ; Netherlands Organization for Scientific Research (NWO) ; Netherlands Organization for Health Research and Development (ZonMw) ; Research Institute for Diseases in the Elderly (RIDE) the Netherlands Genomics Initiative (NGI) ; Netherlands Genomics Initiative (NGI) ; Ministry of Education, Culture and Science ; Ministry of Health Welfare and Sport ; European Commission ; Municipality of Rotterdam ; Wellcome Trust ; Medical Research Council ; Versus Arthritis ; European Union Horizon 2020 ; Chronic Disease Research Foundation (CDRF) ; Zoe Ltd[B13016] ; National Institute for Health Research (NIHR) Clinical Research Network (CRN)[2019M651352] ; Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust[F/07 134/DF] ; King's College London[BB/I021213/1] ; BrightFocus Foundation ; Erasmus University Rotterdam ; [XDB38010400] ; [XDB38020400] ; [XDC01000000] ; [2017SHZDZX01] ; [81930056] ; [31521003] ; [31900408] ; [KFJ-STS-ZDTP-079] ; [22XD1424700] ; [YSBR-077] ; [2015FY111700]
项目资助者	Chinese Academy of Sciences ; Shanghai Municipal Science and Technology Major Project ; National Natural Science Foundation of China (NSFC) ; Science and Technology Service Network Initiative of Chinese Academy of Sciences ; Beijing Advanced Discipline Fund ; CAS Interdisciplinary Innovation Team Project ; Shanghai Science and Technology Commission Excellent Academic Leaders Program ; CAS Project for Young Scientists in Basic Research ; National Science amp; Technology Basic Research Project ; 111 Project ; China Postdoctoral Science Foundation ; Leverhulme Trust ; Biotechnology and Biological Sciences Research Council ; Erasmus MC ; Netherlands Organization for Scientific Research (NWO) ; Netherlands Organization for Health Research and Development (ZonMw) ; Research Institute for Diseases in the Elderly (RIDE) the Netherlands Genomics Initiative (NGI) ; Netherlands Genomics Initiative (NGI) ; Ministry of Education, Culture and Science ; Ministry of Health Welfare and Sport ; European Commission ; Municipality of Rotterdam ; Wellcome Trust ; Medical Research Council ; Versus Arthritis ; European Union Horizon 2020 ; Chronic Disease Research Foundation (CDRF) ; Zoe Ltd ; National Institute for Health Research (NIHR) Clinical Research Network (CRN) ; Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust ; King's College London ; BrightFocus Foundation ; Erasmus University Rotterdam
WOS研究方向	Genetics & Heredity
WOS类目	Genetics & Heredity
WOS记录号	WOS:001038767600001
出版者	PUBLIC LIBRARY SCIENCE
引用统计
文献类型	期刊论文
条目标识符	http://ir.ia.ac.cn/handle/173211/53841
专题	多模态人工智能系统全国重点实验室
通讯作者	Wang, Sijia; Liu, Fan
作者单位	1.Chinese Acad Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Computat Biol, Beijing, Peoples R China 2.Chinese Acad Sci, Beijing Inst Genom, CAS Key Lab Genom & Precis Med, Beijing, Peoples R China 3.Univ Med Ctr, Dept Genet Identificat, Erasmus MC, Rotterdam, Netherlands 4.Univ Med Ctr, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands 5.Shanghai Jiao Tong Univ, BioX Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Minist Educ, Shanghai, Peoples R China 6.Fudan Univ, Human Phenome Inst, Zhangjiang Fudan Int Innovat Ctr, State Key Lab Genet Engn, Shanghai, Peoples R China 7.Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England 8.Beijing 8 High Sch, Beijing, Peoples R China 9.UCL, Dept Genet Evolut & Environm, London, England 10.UCL, UCL Genet Inst, London, England 11.Open Univ, Fac Sci Technol Engn & Math, Sch Math & Stat, Milton Keynes, England 12.Chinese Acad Sci, Inst Automat, Ctr Biometr & Secur Res, Beijing, Peoples R China 13.Chinese Acad Sci, Inst Automat, Natl Lab Pattern Recognit, Beijing, Peoples R China 14.Fudan Univ, Collaborat Innovat Ctr Genet & Dev, Sch Life Sci, Minist Educ,Key Lab Contemporary Anthropol, Shanghai, Peoples R China 15.Univ Chinese Acad Sci, Beijing, Peoples R China 16.Consejo Nacl Invest Cient & Tecn, Inst Patagon Ciencias Sociales & Humanas, Ctr Nacl Patagon, Rosario, Santa Fe, Argentina 17.Univ Fed Rio Grande do Sul, Dept Genet, Porto Alegre, RS, Brazil 18.Natl Sch Anthropol & Hist, Mol Genet Lab, Mexico City, Mexico 19.Univ Nacl Autonoma Mexico, Fac Quim, Unidad Genom Poblac Aplicada Salud, Inst Nacl Med Genom, Mexico City, Mexico 20.Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Labs Invest & Desarrollo, San Martin De Porres, Peru 21.Univ Antioquia, GENMOL Genet Mol, Medellin, Colombia 22.Univ Tarapaca, Inst Alta Invest, Arica, Chile 23.Fudan Taizhou Inst Hlth Sci, Shanghai, Peoples R China 24.Univ Med Ctr, Dept Internal Med, Erasmus MC, Rotterdam, Netherlands 25.Univ Med Ctr, Dept Dermatol, Erasmus MC, Rotterdam, Netherlands 26.Univ Chinese Acad Sci, Sch Artificial Intelligence, Beijing, Peoples R China 27.Aix Marseille Univ, CNRS, EFS, ADES, Marseille, France 28.Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Li, Yi,Xiong, Ziyi,Zhang, Manfei,et al. Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci[J]. PLOS GENETICS,2023,19(7):25.
APA	Li, Yi.,Xiong, Ziyi.,Zhang, Manfei.,Hysi, Pirro G..,Qian, Yu.,...&Liu, Fan.(2023).Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci.PLOS GENETICS,19(7),25.
MLA	Li, Yi,et al."Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci".PLOS GENETICS 19.7(2023):25.