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

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...

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Autores principales: Li, Yi, Xiong, Ziyi, Zhang, Manfei, Hysi, Pirro G., Qian, Yu, Adhikari, Kaustubh, Weng, Jun, Wu, Sijie, Du, Siyuan, Gonzalez-Jose, Rolando, Schuler-Faccini, Lavinia, Bortolini, Maria-Catira, Acuna-Alonzo, Victor, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Wang, Jiucun, Tan, Jingze, Yuan, Ziyu, Jin, Li, Uitterlinden, André G., Ghanbari, Mohsen, Ikram, M. Arfan, Nijsten, Tamar, Zhu, Xiangyu, Lei, Zhen, Jia, Peilin, Ruiz-Linares, Andres, Spector, Timothy D., Wang, Sijia, Kayser, Manfred, Liu, Fan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10351707/
https://www.ncbi.nlm.nih.gov/pubmed/37459304
http://dx.doi.org/10.1371/journal.pgen.1010786
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author Li, Yi
Xiong, Ziyi
Zhang, Manfei
Hysi, Pirro G.
Qian, Yu
Adhikari, Kaustubh
Weng, Jun
Wu, Sijie
Du, Siyuan
Gonzalez-Jose, Rolando
Schuler-Faccini, Lavinia
Bortolini, Maria-Catira
Acuna-Alonzo, Victor
Canizales-Quinteros, Samuel
Gallo, Carla
Poletti, Giovanni
Bedoya, Gabriel
Rothhammer, Francisco
Wang, Jiucun
Tan, Jingze
Yuan, Ziyu
Jin, Li
Uitterlinden, André G.
Ghanbari, Mohsen
Ikram, M. Arfan
Nijsten, Tamar
Zhu, Xiangyu
Lei, Zhen
Jia, Peilin
Ruiz-Linares, Andres
Spector, Timothy D.
Wang, Sijia
Kayser, Manfred
Liu, Fan
author_facet Li, Yi
Xiong, Ziyi
Zhang, Manfei
Hysi, Pirro G.
Qian, Yu
Adhikari, Kaustubh
Weng, Jun
Wu, Sijie
Du, Siyuan
Gonzalez-Jose, Rolando
Schuler-Faccini, Lavinia
Bortolini, Maria-Catira
Acuna-Alonzo, Victor
Canizales-Quinteros, Samuel
Gallo, Carla
Poletti, Giovanni
Bedoya, Gabriel
Rothhammer, Francisco
Wang, Jiucun
Tan, Jingze
Yuan, Ziyu
Jin, Li
Uitterlinden, André G.
Ghanbari, Mohsen
Ikram, M. Arfan
Nijsten, Tamar
Zhu, Xiangyu
Lei, Zhen
Jia, Peilin
Ruiz-Linares, Andres
Spector, Timothy D.
Wang, Sijia
Kayser, Manfred
Liu, Fan
author_sort Li, Yi
collection PubMed
description 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.
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spelling pubmed-103517072023-07-18 Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci Li, Yi Xiong, Ziyi Zhang, Manfei Hysi, Pirro G. Qian, Yu Adhikari, Kaustubh Weng, Jun Wu, Sijie Du, Siyuan Gonzalez-Jose, Rolando Schuler-Faccini, Lavinia Bortolini, Maria-Catira Acuna-Alonzo, Victor Canizales-Quinteros, Samuel Gallo, Carla Poletti, Giovanni Bedoya, Gabriel Rothhammer, Francisco Wang, Jiucun Tan, Jingze Yuan, Ziyu Jin, Li Uitterlinden, André G. Ghanbari, Mohsen Ikram, M. Arfan Nijsten, Tamar Zhu, Xiangyu Lei, Zhen Jia, Peilin Ruiz-Linares, Andres Spector, Timothy D. Wang, Sijia Kayser, Manfred Liu, Fan PLoS Genet Research Article 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. Public Library of Science 2023-07-17 /pmc/articles/PMC10351707/ /pubmed/37459304 http://dx.doi.org/10.1371/journal.pgen.1010786 Text en © 2023 Li et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Li, Yi
Xiong, Ziyi
Zhang, Manfei
Hysi, Pirro G.
Qian, Yu
Adhikari, Kaustubh
Weng, Jun
Wu, Sijie
Du, Siyuan
Gonzalez-Jose, Rolando
Schuler-Faccini, Lavinia
Bortolini, Maria-Catira
Acuna-Alonzo, Victor
Canizales-Quinteros, Samuel
Gallo, Carla
Poletti, Giovanni
Bedoya, Gabriel
Rothhammer, Francisco
Wang, Jiucun
Tan, Jingze
Yuan, Ziyu
Jin, Li
Uitterlinden, André G.
Ghanbari, Mohsen
Ikram, M. Arfan
Nijsten, Tamar
Zhu, Xiangyu
Lei, Zhen
Jia, Peilin
Ruiz-Linares, Andres
Spector, Timothy D.
Wang, Sijia
Kayser, Manfred
Liu, Fan
Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci
title Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci
title_full Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci
title_fullStr Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci
title_full_unstemmed Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci
title_short Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci
title_sort combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10351707/
https://www.ncbi.nlm.nih.gov/pubmed/37459304
http://dx.doi.org/10.1371/journal.pgen.1010786
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