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 ALo SFL for...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 ALo SFL 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 differentiation 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.展开更多
Craniosynostosis is a rare disease in which one or more of the cranial sutures in an infant skull prematurely fuses by turning into bone,with a prevalence of 1 in 2,000—2,500 individuals from reports in Western count...Craniosynostosis is a rare disease in which one or more of the cranial sutures in an infant skull prematurely fuses by turning into bone,with a prevalence of 1 in 2,000—2,500 individuals from reports in Western countries(Wilkie et al.,2017).It may restrict the growth of the brain,leading to some degree of morphological and functional abnormalities,and may affect the neurocognitive function of infants(Lattanzi et al.,2017).Genetic variants underlying craniosynostosis have been identified in cohort studies in Western populations.展开更多
基金Strategic Priority Research Program of Chinese Academy of Sciences(XDB38020400,XDB38010400,XDC01000000)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01,2018SHZDZX01)+5 种基金National Key Research and Development Project(2018YFC0910403)CAS Interdisciplinary Innovation Team ProjectMax Planck-CAS Paul Gerson Unna Independent Research Group Leadership AwardScience and Technology National Natural Science Foundation of China(31900408,81930056)China Postdoctoral Science Foundation(2019M651352,2020M670984)Service Network Initiative of Chinese Academy of Sciences(KFJ-STS-ZDTP-079)。
文摘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 ALo SFL 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 differentiation 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.
基金supported by the foundation of Shanghai municipal commission of Health and Family Planning(20174Y0088)the Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)+1 种基金the CAS Interdisciplinary Innovation Team Projectthe NIHR Oxford Biomedical Research Centre Programme。
文摘Craniosynostosis is a rare disease in which one or more of the cranial sutures in an infant skull prematurely fuses by turning into bone,with a prevalence of 1 in 2,000—2,500 individuals from reports in Western countries(Wilkie et al.,2017).It may restrict the growth of the brain,leading to some degree of morphological and functional abnormalities,and may affect the neurocognitive function of infants(Lattanzi et al.,2017).Genetic variants underlying craniosynostosis have been identified in cohort studies in Western populations.
