Facial and cranial variation represent a multidimensional set of highly correlated and heritable phenotypes.Little is known about the genetic basis explaining this correlation.We develop a software package ALoSFL for simultaneous localization of facial and cranial landmarks from head computed tomography(CT)images,apply it in the analysis of head CT images of 777 Han Chinese women,and obtain a set of phenotypes representing variation in face,skull and facial soft tissue thickness(FSTT).Association analysis of 301 single nucleotide polymorphisms(SNPs)from 191 distinct genomic loci previously associated with facial variation reveals an unexpected larger number of loci showing significant associations(P＜1e-3)with cranial phenotypes than expected under the null(O/E=3.39),suggesting facial and cranial phenotypes share a substantial proportion of genetic components.Adding FSTT to a SNP-only model shows a large impact in explaining facial variance.A gene ontology analysis reveals that bone morphogenesis and osteoblast dif-ferentiation likely underlie our cranial-significant findings.Overall,this study simultaneously investigates the genetic effects on both facial and cranial variation of the same sample,supporting that facial variation is a composite phenotype of cranial variation and FSTT.

Wei Qian;Manfei Zhang;Kaiwen Wan;Yunxia Xie;Siyuan Du;Jiarui Li;Xiongzheng Mu;Jiange Qiu;Xiangyang Xue;Xiahai Zhuang;Yingzhi Wu;Fan Liu;Sijia Wang

State Key Laboratory of Genetic Engineering,Human Phenome Institute,Zhangjiang Fudan International Innovation Center,Fudan University,Shanghai 201203,China;School of Computer Science,Fudan University,Shanghai 200438,China;CAS Key Laboratory of Computational Biology,Shanghai Institute of Nutrition and Health,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai 200031,China;School of Data Science,Fudan University,Shanghai 200433,China;Academy of Medical Science,Zhengzhou University,Zhengzhou,Henan 450052,China;Department of Plastic Surgery,Huashan Hospital,Fudan University,Shanghai 200040,China;CAS Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,University of Chinese Academy of Sciences,Beijing 100101,China;School of Future Technology,University of Chinese Academy of Sciences,Beijing 101408,China;Center for Excellence in Animal Evolution and Genetics,Chinese Academy of Sciences,Kunming,Yunnan 650223,China

遗传学报

[1]Wei Qian;Manfei Zhang;Kaiwen Wan;Yunxia Xie;Siyuan Du;Jiarui Li;Xiongzheng Mu;Jiange Qiu;Xiangyang Xue;Xiahai Zhuang;Yingzhi Wu;Fan Liu;Sijia Wang-.Genetic evidence for facial variation being a composite phenotype of cranial variation and facial soft tissue thickness)[J].遗传学报,2022(10):934-942

ALoSFL,FSTT

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