The past two decades have witnessed a revolution in identifying genetic risk factors underlying diseases and complex traits using genome-wide association studies （GWAS） （Risch and Merikangas, 1996; Hirschhom and Da...The past two decades have witnessed a revolution in identifying genetic risk factors underlying diseases and complex traits using genome-wide association studies （GWAS） （Risch and Merikangas, 1996; Hirschhom and Daly, 2005; Altshuler et al., 2008）. Together with advanced high-throughput technologies for genotyping and sequencing, GWAS have discovered thousands of susceptibility loci for various traits （Welter et al., 2014）.展开更多
Growth is the developmental process involving important genetic components.Functional mapping(FunMap)has been used as an approach to map quantitative trait loci(QTLs)governing growth trajectories by incorporating grow...Growth is the developmental process involving important genetic components.Functional mapping(FunMap)has been used as an approach to map quantitative trait loci(QTLs)governing growth trajectories by incorporating growth equations.FunMap is based on reductionism thinking,with a power to identify a small set of significant QTLs from the whole pool of genome-wide markers.Yet,increasing evidence shows that a complex trait is controlled by all genes the organism may possibly carry.Here,we describe and demonstrate a different mapping approach that encapsulates all markers into genetic interaction networks.This approach,symbolized as FunGraph,combines functional mapping,evolutionary game theory,and prey-predator theory into mathematical graphs,allowing the observed genetic effect of a locus to be decomposed into its independent component(resulting from this locus’intrinsic capacity)and dependent component(due to extrinsic regulation by other loci).Using FunGraph,we can visualize and trace the roadmap of how each locus interact with every other locus to impact growth.In a population-based association study of Euphrates poplar,we use FunGraph to identify the previously neglected genetic interaction effects that contribute to the genetic architecture of juvenile stem growth.FunGraph could open up a novel gateway to comprehend the global genetic control mechanisms of complex traits.展开更多
Willow(Salix)is one of the most important ornamental tree species in landscape plants.One species,Salix matsudana,is widely used as a shade tree and border tree because of its soft branches and plump crown.Some variet...Willow(Salix)is one of the most important ornamental tree species in landscape plants.One species,Salix matsudana,is widely used as a shade tree and border tree because of its soft branches and plump crown.Some varieties of S.matsudana were salt tolerant and could grow normally in coastal regions.However,the molecular mechanisms of salt tolerance for S.matsudana have been less clear.Here,we addressed this issue by performing a mapping experiment containing 195 intraspecific F1 progeny of S.matsudana,derived from salt-sensitive‘yanjiang’and salt-tolerant‘9901’,grown by cuttings in a 100 mM NaCl solution.Growth performance of these progeny under salt stress was investigated,displaying marked genotypic variability with the coefficients of variance of 28.64–86.11%in shoot and root growth traits.We further mapped specific QTLs contributing to these differences to the Salix genome.Of the 204 QTLs identified,a few were detected to explain a remarkably larger portion of the phenotypic variation than many others.Many detected QTLs were found to reside in the region of candidate genes of known biological function.The discovery of growth QTLs expressed under salt stress provides important information for marker-assisted breeding of salt tolerant Salix varieties and founds the basis for the application of S.matsudana in coastal afforestation.展开更多
BACKGROUND Type 1 diabetes(T1D)is a complex disease with a higher incidence in Europeans than other populations.The Colombians Living in Medellin(CLM)is admixed with ancestry contributions from Europeans,Native Americ...BACKGROUND Type 1 diabetes(T1D)is a complex disease with a higher incidence in Europeans than other populations.The Colombians Living in Medellin(CLM)is admixed with ancestry contributions from Europeans,Native Americans(NAT)and Africans(AFR).AIM Our aim was to analyze the genetic admixture component at candidate T1D loci in Colombian individuals with the disease.METHODS Seventy-four ancestry informative markers(AIMs),which tagged 41 T1D candidate loci/genes,were tested by studying a cohort of 200 Northwest Colombia diseased individuals.T1D status was classified by testing for glutamic acid decarboxylase(GAD-65 kDa)and protein tyrosine-like antigen-2 autoantibodies in serum samples.Candidate loci/genes included HLA,INS,PTPN22,CTLA4,IL2RA,SUMO4,CLEC16A,IFIH1,EFR3B,IL7R,NRP1 and RNASEH1,amongst others.The 1,000 genome database was used to analyze data from 94 individuals corresponding to the reference CLM.As the data did not comply with a normal distribution,medians were compared between groups using the Mann-Whitney U-test.RESULTS Both T1D patients and individuals from CLM displayed mainly European ancestry(61.58 vs 62.06)followed by Native American(27.34 vs 27.46)and to a lesser extent the AFR ancestry(10.28 vs 10.65)components.However,compared to CLM,ancestry of T1D patients displayed a decrease of NAT ancestry at gene EFR3B(24.30 vs 37.10)and an increase at genes IFIH1(32.07 vs 14.99)and IL7R(52.18 vs 39.18).Also,for gene NRP1(36.67 vs 0.003),we observed a non-AFR contribution(attributed to NAT).Autoimmune patients(positive for any of two auto-antibodies)displayed lower NAT ancestry than idiopathic patients at the MHC region(20.36 vs 31.88).Also,late onset patients presented with greater AFR ancestry than early onset patients at gene IL7R(19.96 vs 6.17).An association analysis showed that,even after adjusting for admixture,an association exists for at least seven such AIMs,with the strongest findings on chromosomes 5 and 10(gene IL7R,P=5.56×10-6 and gene NRP1,P=8.70×10-19,respectively).CONCLUSION Although Colombian T1D patients have globally presented with higher European admixture,specific T1D loci have displayed varying levels of Native American and AFR ancestries in diseased individuals.展开更多
Selection of beneficial genomic variants was crucial for regional adaptation of crops during domestication,but the underlying genomic basis remains largely unexplored.Here we report a genome-wide selective-sweep analy...Selection of beneficial genomic variants was crucial for regional adaptation of crops during domestication,but the underlying genomic basis remains largely unexplored.Here we report a genome-wide selective-sweep analysis of 655 japonica and 1,205 indica accessions selected from 2,673 landraces through principal component analysis to identify 5,636 non-synonymous single nucleotide polymorphisms(SNPs)fixed in at least one subspecies.We classified these SNPs into three groups,jiS(japonica-and indica-selected),jS(japonica-selected only),and iS(indica-selected only),and documented evidence for selection acting on these groups,their relation to yield-related traits,such as heading date,and their practical value in cropping area prediction.We also demonstrated the role of a jiS-SNP-containing gene in temperature adaptability.Our study informs genes underpinning adaptation that may shape Green Super Rice and proposes a time-saving,cost-reducing selection strategy of genomic breeding,sweep-SNP-guided selection,for developing regionally-adapted heterosis.展开更多
Triploids,recognized to occur more frequently in natural and experimental populations of many species than previously appreciated,display important economic and biological values.Despite this,however,linkage analysis ...Triploids,recognized to occur more frequently in natural and experimental populations of many species than previously appreciated,display important economic and biological values.Despite this,however,linkage analysis for triploids has not been well explored.We develop a statistical model for estimating and testing the linkage between molecular markers in a triploid population derived from a tetraploid and diploid parent.The model incorporates one important meiotic feature of tetraploids by which more homologous chromosomes pair with a greater likelihood than less homologous chromosomes.By implementing the EM algorithm within the maximum likelihood framework,the model provides a procedure for simultaneous estimation of the linkage and preferential pairing factor.The model accommodates the segregating patterns of pseudotest markers and intercross markers with different amounts of informativeness.The utility of the model was validated through a real data analysis and simulation studies.The model provides a statistical tool for linkage analysis in a triploid population by taking into account meiotic behavior of tetraploids.Results from the model will help to shed light on the genetic diversity and origin of a polyploid population.展开更多
Background:Genome-wide association studies(GWASs)have identified thousands of genetic variants that are associated with many complex traits.However,their biological mechanisms remain largely unknown.Transcriptome-wide...Background:Genome-wide association studies(GWASs)have identified thousands of genetic variants that are associated with many complex traits.However,their biological mechanisms remain largely unknown.Transcriptome-wide association studies(TWAS)have been recently proposed as an invaluable tool for investigating the potential gene regulatory mechanisms underlying variant-trait associations.Specifically,TWAS integrate GWAS with expression mapping studies based on a common set of variants and aim to identify genes whose GReX is associated with the phenotype.Various methods have been developed for performing TWAS and/or similar integrative analysis.Each such method has a different modeling assumption and many were initially developed to answer different biological questions.Consequently,it is not straightforward to understand their modeling property from a theoretical perspective.Results:We present a technical review on thirteen TWAS methods.Importantly,we show that these methods can all be viewed as two-sample Mendelian randomization(MR)analysis,which has been widely applied in GWASs for examining the causal effects of exposure on outcome.Viewing different TWAS methods from an MR perspective provides us a unique angle for understanding their benefits and pitfalls.We systematically introduce the MR analysis framework,explain how features of the GWAS and expression data influence the adaptation of MR for TWAS,and re-interpret the modeling assumptions made in different TWAS methods from an MR angle.We finally describe future directions for TWAS methodology development.Conclusions:We hope that this review would serve as a useful reference for both methodologists who develop TWAS methods and practitioners who perform TWAS analysis.展开更多
Background:The prevalence of skin diseases and diabetes mellitus(DM)are prominent around the world.The current scope of knowledge regarding the prevalence of skin diseases and comorbidities with type 2 DM(T2DM)is limi...Background:The prevalence of skin diseases and diabetes mellitus(DM)are prominent around the world.The current scope of knowledge regarding the prevalence of skin diseases and comorbidities with type 2 DM(T2DM)is limited,leading to limited recognition of the correlations between skin diseases and T2DM.Methods:We collected 383 subjects from the Da Qing Diabetes Study during the period from July 9th to September 1st,2016.The subjects were categorized into three groups:Normal glucose tolerance(NGT),impaired glucose tolerance(IGT),and T2DM.The prevalence and clinical characteristics of skin diseases were recorded and investigated.Results:In this cross-sectional study,383 individuals with ages ranging from 53 to 89-year-old were recruited.The overall prevalence of skin diseases was 93.5%,and 75.7%of individuals had two or more kinds of skin diseases.Additionally,there were 47 kinds of comorbid skin diseases in patients with T2DM,of which eight kinds of skin diseases had a prevalence>10%.The prevalence of skin diseases in NGT,IGT,and T2DM groups were 93.3%,91.5%,and 96.6%,respectively;stratified analysis by categories showed a statistically significant difference in"disturbances of pigmentation"and"neurological and psychogenic dermatoses".The duration of T2DM also significantly associated with the prevalence of"disturbances of pigmentation"and"neurological and psychogenic dermatoses".Subsequently,the prevalence of"disturbances of pigmentation"was higher in males than females in NGT(P<0.01)and T2DM(P<0.01)groups.In addition,the difference in the prevalence of"disturbances of pigmentation"was also significant in NGT and T2DM groups(P<0.01).Conclusions:There was a high prevalence of skin diseases in the Da Qing Diabetes Study.To address the skin diseases in the Da Qing Diabetes Study,increased awareness and intervention measures should be implemented.展开更多
Nonlinear mixed-eirects (NLME) modek have become popular in various disciplines over the past several decades.However,the existing methods for parameter estimation imple-mented in standard statistical packages such as...Nonlinear mixed-eirects (NLME) modek have become popular in various disciplines over the past several decades.However,the existing methods for parameter estimation imple-mented in standard statistical packages such as SAS and R/S-Plus are generally limited k) single-or multi-level NLME models that only allow nested random effects and are unable to cope with crossed random effects within the framework of NLME modeling.In t his study,wc propose a general formulation of NLME models that can accommodate both nested and crassed random effects,and then develop a computational algorit hm for parameter estimation based on normal assumptions.The maximum likelihood estimation is carried out using the first-order conditional expansion (FOCE) for NLME model linearization and sequential quadratic programming (SCJP) for computational optimization while ensuring positive-definiteness of the estimated variance-covariance matrices of both random effects and error terms.The FOCE-SQP algorithm is evaluated using the height and diameter data measured on trees from Korean larch (L.olgeiisis var,Chang-paienA.b) experimental plots aa well as simulation studies.We show that the FOCE-SQP method converges fast with high accuracy.Applications of the general formulation of NLME models are illustrated with an analysis of the Korean larch data.展开更多
Background:Previously rare A2ML1 variants were identified to confer otitis media susceptibility in an indigenous Filipino community and in otitis-prone US children.The goal of this study is to describe differences in ...Background:Previously rare A2ML1 variants were identified to confer otitis media susceptibility in an indigenous Filipino community and in otitis-prone US children.The goal of this study is to describe differences in the middle ear microbiome between carriers and non-carriers of an A2ML1 duplication variant that increases risk for chronic otitis media among indigenous Filipinos with poor health care access.Methods:Ear swabs were obtained from 16 indigenous Filipino individuals with chronic otitis media,of whom 11 carry the A2ML1 duplication variant.Ear swabs were submitted for 16S rRNA gene sequencing.Results:Genotype-based differences in microbial richness,structure,and composition were identified,but were not statistically significant.Taxonomic analysis revealed that the relative abundance of the phyla Fusobacteria and Bacteroidetes,and genus Fusobacterium were nominally increased in carriers compared to non-carriers,but were non-significant after correction for multiple testing.We also detected rare bacteria including Oligella that was reported only once in the middle ear.Conclusions:These findings suggest that A2ML1-related otitis media susceptibility may be mediated by changes in the middle ear microbiome.Knowledge of middle ear microbial profiles according to genetic background can be potentially useful for therapeutic and prophylactic interventions for otitis media and can guide public health interventions towards decreasing otitis media prevalence within the indigenous Filipino community.展开更多
Adaptive cluster sampling （ACS） has been widely used for data collection of environment and natural resources. However, the randomness of its final sample size often impedes the use of this method. To control the fi...Adaptive cluster sampling （ACS） has been widely used for data collection of environment and natural resources. However, the randomness of its final sample size often impedes the use of this method. To control the final sample sizes, in this study, a k-step ACS based on Horvitz-Thompson （HT） estimator was developed and an unbiased estimator was derived. The k-step ACS-HT was assessed first using a simulated example and then using a real survey for numbers of plants for three species that were characterized by clustered and patchily spatial distributions. The effectiveness of this sampling design method was assessed in comparison with ACS Hansen-Hurwitz （ACS-HH） and ACS- HT estimators, and k-step ACS-HT estimator. The effectiveness of using different k- step sizes was also compared. The results showed that k-step ACS^HT estimator was most effective and ACS-HH was the least. Moreover, stable sample mean and variance estimates could be obtained after a certain number of steps, but depending on plant species, k-step ACS without replacement was slightly more effective than that with replacement. In k-step ACS, the variance estimate of one-step ACS is much larger than other k-step ACS （k 〉 1）, but it is smaller than ACS. This implies that k-step ACS is more effective than traditional ACS, besides, the final sample size can be controlled easily in population with big clusters.展开更多
基金supported by the Fundamental Research Funds for the Central Universities (BLX2013026)the National Natural Science Foundation of China (No. 31470675)+2 种基金the National Institutes of Health (K01AA023321)supported by the National Heart, Lung, and Blood Institute in collaboration with Boston University (Contract No. N01-HC-25195)Funding for SHARe Affymetrix genotyping was provided by NHLBI Contract N02-HL-64278
文摘The past two decades have witnessed a revolution in identifying genetic risk factors underlying diseases and complex traits using genome-wide association studies （GWAS） （Risch and Merikangas, 1996; Hirschhom and Daly, 2005; Altshuler et al., 2008）. Together with advanced high-throughput technologies for genotyping and sequencing, GWAS have discovered thousands of susceptibility loci for various traits （Welter et al., 2014）.
文摘Growth is the developmental process involving important genetic components.Functional mapping(FunMap)has been used as an approach to map quantitative trait loci(QTLs)governing growth trajectories by incorporating growth equations.FunMap is based on reductionism thinking,with a power to identify a small set of significant QTLs from the whole pool of genome-wide markers.Yet,increasing evidence shows that a complex trait is controlled by all genes the organism may possibly carry.Here,we describe and demonstrate a different mapping approach that encapsulates all markers into genetic interaction networks.This approach,symbolized as FunGraph,combines functional mapping,evolutionary game theory,and prey-predator theory into mathematical graphs,allowing the observed genetic effect of a locus to be decomposed into its independent component(resulting from this locus’intrinsic capacity)and dependent component(due to extrinsic regulation by other loci).Using FunGraph,we can visualize and trace the roadmap of how each locus interact with every other locus to impact growth.In a population-based association study of Euphrates poplar,we use FunGraph to identify the previously neglected genetic interaction effects that contribute to the genetic architecture of juvenile stem growth.FunGraph could open up a novel gateway to comprehend the global genetic control mechanisms of complex traits.
基金This work was supported by‘Jiangsu Agriculture Science and Technology Innovation Fund(JASTIF),CX(16)1005)’Research&Development Programme in Jiangsu Province(Modern Agriculture)(No.BE2016328)+2 种基金the Fund for 333 Engineering Project in Jiangsu Province(No.BRA2015125)‘the Fund for the 12th Six Peak Talent Project in Jiangsu Province(No.2015-NY-042)’‘the Fund for 226 Engineering Project in Nantong City(No.2014008)’。
文摘Willow(Salix)is one of the most important ornamental tree species in landscape plants.One species,Salix matsudana,is widely used as a shade tree and border tree because of its soft branches and plump crown.Some varieties of S.matsudana were salt tolerant and could grow normally in coastal regions.However,the molecular mechanisms of salt tolerance for S.matsudana have been less clear.Here,we addressed this issue by performing a mapping experiment containing 195 intraspecific F1 progeny of S.matsudana,derived from salt-sensitive‘yanjiang’and salt-tolerant‘9901’,grown by cuttings in a 100 mM NaCl solution.Growth performance of these progeny under salt stress was investigated,displaying marked genotypic variability with the coefficients of variance of 28.64–86.11%in shoot and root growth traits.We further mapped specific QTLs contributing to these differences to the Salix genome.Of the 204 QTLs identified,a few were detected to explain a remarkably larger portion of the phenotypic variation than many others.Many detected QTLs were found to reside in the region of candidate genes of known biological function.The discovery of growth QTLs expressed under salt stress provides important information for marker-assisted breeding of salt tolerant Salix varieties and founds the basis for the application of S.matsudana in coastal afforestation.
基金Colciencias-Colombia grant No.111556933366CODI-Universidad de Antioquia,and Scholarship from Colciencias,call No.727(from2015)
文摘BACKGROUND Type 1 diabetes(T1D)is a complex disease with a higher incidence in Europeans than other populations.The Colombians Living in Medellin(CLM)is admixed with ancestry contributions from Europeans,Native Americans(NAT)and Africans(AFR).AIM Our aim was to analyze the genetic admixture component at candidate T1D loci in Colombian individuals with the disease.METHODS Seventy-four ancestry informative markers(AIMs),which tagged 41 T1D candidate loci/genes,were tested by studying a cohort of 200 Northwest Colombia diseased individuals.T1D status was classified by testing for glutamic acid decarboxylase(GAD-65 kDa)and protein tyrosine-like antigen-2 autoantibodies in serum samples.Candidate loci/genes included HLA,INS,PTPN22,CTLA4,IL2RA,SUMO4,CLEC16A,IFIH1,EFR3B,IL7R,NRP1 and RNASEH1,amongst others.The 1,000 genome database was used to analyze data from 94 individuals corresponding to the reference CLM.As the data did not comply with a normal distribution,medians were compared between groups using the Mann-Whitney U-test.RESULTS Both T1D patients and individuals from CLM displayed mainly European ancestry(61.58 vs 62.06)followed by Native American(27.34 vs 27.46)and to a lesser extent the AFR ancestry(10.28 vs 10.65)components.However,compared to CLM,ancestry of T1D patients displayed a decrease of NAT ancestry at gene EFR3B(24.30 vs 37.10)and an increase at genes IFIH1(32.07 vs 14.99)and IL7R(52.18 vs 39.18).Also,for gene NRP1(36.67 vs 0.003),we observed a non-AFR contribution(attributed to NAT).Autoimmune patients(positive for any of two auto-antibodies)displayed lower NAT ancestry than idiopathic patients at the MHC region(20.36 vs 31.88).Also,late onset patients presented with greater AFR ancestry than early onset patients at gene IL7R(19.96 vs 6.17).An association analysis showed that,even after adjusting for admixture,an association exists for at least seven such AIMs,with the strongest findings on chromosomes 5 and 10(gene IL7R,P=5.56×10-6 and gene NRP1,P=8.70×10-19,respectively).CONCLUSION Although Colombian T1D patients have globally presented with higher European admixture,specific T1D loci have displayed varying levels of Native American and AFR ancestries in diseased individuals.
基金supported by the National Key Program on Transgenic Research from the Ministry of Agriculture of China(2016ZX08009002-003-003)Natural Science Foundation of Guangdong Province of China(2015A030313414)Science and Technology Program of Guangzhou,China(201607010196)。
文摘Selection of beneficial genomic variants was crucial for regional adaptation of crops during domestication,but the underlying genomic basis remains largely unexplored.Here we report a genome-wide selective-sweep analysis of 655 japonica and 1,205 indica accessions selected from 2,673 landraces through principal component analysis to identify 5,636 non-synonymous single nucleotide polymorphisms(SNPs)fixed in at least one subspecies.We classified these SNPs into three groups,jiS(japonica-and indica-selected),jS(japonica-selected only),and iS(indica-selected only),and documented evidence for selection acting on these groups,their relation to yield-related traits,such as heading date,and their practical value in cropping area prediction.We also demonstrated the role of a jiS-SNP-containing gene in temperature adaptability.Our study informs genes underpinning adaptation that may shape Green Super Rice and proposes a time-saving,cost-reducing selection strategy of genomic breeding,sweep-SNP-guided selection,for developing regionally-adapted heterosis.
基金supported by Fundamental Research Funds for the Central Universities(YX2011-30,YX2010-30,BLYX200924and JD2010-5)Special Fund for Forestry-Scientific Research in the Public Interest(201004017)+4 种基金National Natural Science Foundation of China(61170268)China Agricultural Research System-CARSNSF/IOS-0923975Changjiang Scholars Award"Thousand-person Plan"Award
文摘Triploids,recognized to occur more frequently in natural and experimental populations of many species than previously appreciated,display important economic and biological values.Despite this,however,linkage analysis for triploids has not been well explored.We develop a statistical model for estimating and testing the linkage between molecular markers in a triploid population derived from a tetraploid and diploid parent.The model incorporates one important meiotic feature of tetraploids by which more homologous chromosomes pair with a greater likelihood than less homologous chromosomes.By implementing the EM algorithm within the maximum likelihood framework,the model provides a procedure for simultaneous estimation of the linkage and preferential pairing factor.The model accommodates the segregating patterns of pseudotest markers and intercross markers with different amounts of informativeness.The utility of the model was validated through a real data analysis and simulation studies.The model provides a statistical tool for linkage analysis in a triploid population by taking into account meiotic behavior of tetraploids.Results from the model will help to shed light on the genetic diversity and origin of a polyploid population.
基金the National Institutes of Health(NIH)Grants RO1HG009124 and the National Science Foundation(NSF)Grant DMS1712933.
文摘Background:Genome-wide association studies(GWASs)have identified thousands of genetic variants that are associated with many complex traits.However,their biological mechanisms remain largely unknown.Transcriptome-wide association studies(TWAS)have been recently proposed as an invaluable tool for investigating the potential gene regulatory mechanisms underlying variant-trait associations.Specifically,TWAS integrate GWAS with expression mapping studies based on a common set of variants and aim to identify genes whose GReX is associated with the phenotype.Various methods have been developed for performing TWAS and/or similar integrative analysis.Each such method has a different modeling assumption and many were initially developed to answer different biological questions.Consequently,it is not straightforward to understand their modeling property from a theoretical perspective.Results:We present a technical review on thirteen TWAS methods.Importantly,we show that these methods can all be viewed as two-sample Mendelian randomization(MR)analysis,which has been widely applied in GWASs for examining the causal effects of exposure on outcome.Viewing different TWAS methods from an MR perspective provides us a unique angle for understanding their benefits and pitfalls.We systematically introduce the MR analysis framework,explain how features of the GWAS and expression data influence the adaptation of MR for TWAS,and re-interpret the modeling assumptions made in different TWAS methods from an MR angle.We finally describe future directions for TWAS methodology development.Conclusions:We hope that this review would serve as a useful reference for both methodologists who develop TWAS methods and practitioners who perform TWAS analysis.
基金supported by grants from the Milstein Medical Asian American Partnership Foundation Research Project"Establishment and application of digital image database for skin diseases in the Chinese population"(No.MMAAP2016023)the Open Research Funding of China Skin Image Database(Nos.CSID-ORF-201711 and CSID-ORF-201918)+3 种基金the Fundamental Research Funds for the Central Universities(No.3332018182)Innovation Fund for Graduate Students(No.2018-1002-01-26)Peking Union Medical College,Chinaand the scholarship from China Scholarship Council(No.201806210430)。
文摘Background:The prevalence of skin diseases and diabetes mellitus(DM)are prominent around the world.The current scope of knowledge regarding the prevalence of skin diseases and comorbidities with type 2 DM(T2DM)is limited,leading to limited recognition of the correlations between skin diseases and T2DM.Methods:We collected 383 subjects from the Da Qing Diabetes Study during the period from July 9th to September 1st,2016.The subjects were categorized into three groups:Normal glucose tolerance(NGT),impaired glucose tolerance(IGT),and T2DM.The prevalence and clinical characteristics of skin diseases were recorded and investigated.Results:In this cross-sectional study,383 individuals with ages ranging from 53 to 89-year-old were recruited.The overall prevalence of skin diseases was 93.5%,and 75.7%of individuals had two or more kinds of skin diseases.Additionally,there were 47 kinds of comorbid skin diseases in patients with T2DM,of which eight kinds of skin diseases had a prevalence>10%.The prevalence of skin diseases in NGT,IGT,and T2DM groups were 93.3%,91.5%,and 96.6%,respectively;stratified analysis by categories showed a statistically significant difference in"disturbances of pigmentation"and"neurological and psychogenic dermatoses".The duration of T2DM also significantly associated with the prevalence of"disturbances of pigmentation"and"neurological and psychogenic dermatoses".Subsequently,the prevalence of"disturbances of pigmentation"was higher in males than females in NGT(P<0.01)and T2DM(P<0.01)groups.In addition,the difference in the prevalence of"disturbances of pigmentation"was also significant in NGT and T2DM groups(P<0.01).Conclusions:There was a high prevalence of skin diseases in the Da Qing Diabetes Study.To address the skin diseases in the Da Qing Diabetes Study,increased awareness and intervention measures should be implemented.
基金The authors would like to thank the Thirteenth Five-year Plan Pioneering project of High Technology Plan of the National Department of Technology (No. 2017YFC0504101)the National Natural Science Foundations of China (Nos. 31470641, 31300534 and 31570628) for the financial support of this study.
文摘Nonlinear mixed-eirects (NLME) modek have become popular in various disciplines over the past several decades.However,the existing methods for parameter estimation imple-mented in standard statistical packages such as SAS and R/S-Plus are generally limited k) single-or multi-level NLME models that only allow nested random effects and are unable to cope with crossed random effects within the framework of NLME modeling.In t his study,wc propose a general formulation of NLME models that can accommodate both nested and crassed random effects,and then develop a computational algorit hm for parameter estimation based on normal assumptions.The maximum likelihood estimation is carried out using the first-order conditional expansion (FOCE) for NLME model linearization and sequential quadratic programming (SCJP) for computational optimization while ensuring positive-definiteness of the estimated variance-covariance matrices of both random effects and error terms.The FOCE-SQP algorithm is evaluated using the height and diameter data measured on trees from Korean larch (L.olgeiisis var,Chang-paienA.b) experimental plots aa well as simulation studies.We show that the FOCE-SQP method converges fast with high accuracy.Applications of the general formulation of NLME models are illustrated with an analysis of the Korean larch data.
基金supported by:the National Organization for Hearing Research Foundation,the Hearing Health Foundation,and Action On Hearing Loss(to R.L.P.S.C.)the University of the Philippines Manila–National Institutes of Health(to G.T.A.)+1 种基金the Albert and Margaret Alkek Foundation(to J.F.P.)the United States National Institutes of Health-National Institute on Deafness and Other Communication Disorders grants K18 DC013564(to T.C.),R01 DC011651 and R01 DC003594(to S.M.L.)and R01 DC015004(to R.L.P.S.C.).
文摘Background:Previously rare A2ML1 variants were identified to confer otitis media susceptibility in an indigenous Filipino community and in otitis-prone US children.The goal of this study is to describe differences in the middle ear microbiome between carriers and non-carriers of an A2ML1 duplication variant that increases risk for chronic otitis media among indigenous Filipinos with poor health care access.Methods:Ear swabs were obtained from 16 indigenous Filipino individuals with chronic otitis media,of whom 11 carry the A2ML1 duplication variant.Ear swabs were submitted for 16S rRNA gene sequencing.Results:Genotype-based differences in microbial richness,structure,and composition were identified,but were not statistically significant.Taxonomic analysis revealed that the relative abundance of the phyla Fusobacteria and Bacteroidetes,and genus Fusobacterium were nominally increased in carriers compared to non-carriers,but were non-significant after correction for multiple testing.We also detected rare bacteria including Oligella that was reported only once in the middle ear.Conclusions:These findings suggest that A2ML1-related otitis media susceptibility may be mediated by changes in the middle ear microbiome.Knowledge of middle ear microbial profiles according to genetic background can be potentially useful for therapeutic and prophylactic interventions for otitis media and can guide public health interventions towards decreasing otitis media prevalence within the indigenous Filipino community.
文摘Adaptive cluster sampling （ACS） has been widely used for data collection of environment and natural resources. However, the randomness of its final sample size often impedes the use of this method. To control the final sample sizes, in this study, a k-step ACS based on Horvitz-Thompson （HT） estimator was developed and an unbiased estimator was derived. The k-step ACS-HT was assessed first using a simulated example and then using a real survey for numbers of plants for three species that were characterized by clustered and patchily spatial distributions. The effectiveness of this sampling design method was assessed in comparison with ACS Hansen-Hurwitz （ACS-HH） and ACS- HT estimators, and k-step ACS-HT estimator. The effectiveness of using different k- step sizes was also compared. The results showed that k-step ACS^HT estimator was most effective and ACS-HH was the least. Moreover, stable sample mean and variance estimates could be obtained after a certain number of steps, but depending on plant species, k-step ACS without replacement was slightly more effective than that with replacement. In k-step ACS, the variance estimate of one-step ACS is much larger than other k-step ACS （k 〉 1）, but it is smaller than ACS. This implies that k-step ACS is more effective than traditional ACS, besides, the final sample size can be controlled easily in population with big clusters.
