实现全基因组关联研究(Genome-wide association study,GWA)在数年前还是遗传学家们的梦想,如今它已经变成了现实。自2005年Science杂志报道了第一项有关年龄相关性(视网膜)黄斑变性全基因组关联研究研究以来,有关与复杂疾病的全基因组...实现全基因组关联研究(Genome-wide association study,GWA)在数年前还是遗传学家们的梦想,如今它已经变成了现实。自2005年Science杂志报道了第一项有关年龄相关性(视网膜)黄斑变性全基因组关联研究研究以来,有关与复杂疾病的全基因组关联研究如雨后春笋般层出不穷。文中介绍了近两年来全基因组关联研究在复杂疾病研究领域内的主要发现、全基因组关联研究设计原理、遗传标记的选择、比较及相关商品信息。最后介绍了人类基因组拷贝数变异的研究进展,总结了人类全基因组关联研究所取得成就和存在的问题,并对全基因组关联研究未来的研究重点和要解决的问题进行了展望。展开更多
Objective To develop a nationally acceptable blood pressure(BP)reference standards for the diagnosis and evaluation of hypertension in children and adolescents in China.Methods The current study was based on the data ...Objective To develop a nationally acceptable blood pressure(BP)reference standards for the diagnosis and evaluation of hypertension in children and adolescents in China.Methods The current study was based on the data from eleven large-scale cross-sectional BP surveys in China's Mainland since 2001,the survey sites were representative of national geographical distribution including four municipalities(Beijing,Shanghai,Tianjin,Chongqing)and seven provinces(Hunan,Liaoning,Hebei,Zhejiang,Guangxi,Xinqiang and Guangdong).The surveys which met the following selection criteria were involved to form the reference population sample and pooled database:1)Subjects were Han nationality and their ages were from 3 to 18 years old;2)BP levels were measured by auscultation using standard sphygmomanometer and recorded as Korotkoff phase 1(SBP),Korotkoff phase 4(DBP-K4)and/or Korotkoff phase 5(DBP-K5);3)All surveyors were trained before investigations and standard quality control was implemented throughout the BP measuring process;4)Basic variables,except BPs,were at least included but not limited to age,sex,nationality,height and weight.Totally 112 227 subjects(56 912 males accounting for 50.7%)were enrolled in the reference population sample in this study.SPSS 13.0 software was used to do the descriptive statistical analysis.Centile curves for SBP,DBP-K4 and DBP-K5 were drawn by sex using LMS method.Z scores of Height and BMI were calculated based on the data from the Chinese National Survey on Constitution and Health(CNSCH)in schoolchildren in 2005 to evaluate the nutrition status and development level of the reference population.Results The reference population had an optimal representation of Chinese Han children and adolescents.The resulting curves provided specific cut off points based on age and sex for the diagnosis of high normal BP,hypertension and severe hypertension,respectively.Given the best approach for blood pressure measurement in children and adolescents remained controversial,especially on the choice of K4 or K5 for diastolic blood pressure.So in present study we showed DBP reference standards with K4 and K5,respectively,that is,two sets of SBP/DBP-K4 and SBP/DBP-K5 were developed for the flexible usage in practice.The proposed reference standards of SBP/DBP-K4 were similar to the US fourth report on the diagnosis,evaluation,and treatment of high blood pressure in children and adolescents,with only exception of the age groups of preschool children and late adolescence.Cut off points for hypertension using DBP-K5 were significantly lower than the US standards.Conclusions The proposed reference standards,which were firstly developed based on the most recently pooled national data and in line with the growth and development characteristics of Chinese children and adolescents,should help for the early screening,diagnosis and evaluation of hypertension in children and adolescents,and were also recommended to be used in national comparisons of prevalence of hypertension.展开更多
1项目负责人曹云：复旦大学附属儿科医院新生儿科；Vibhuti Shah、Shoo K Lee：加拿大多伦多大学，加拿大Mount Sinai医院；王卫平：复旦大学100,40,20,10]2 资助者本研究方案获得美国中华医学基金会（China Medical Board,CMB）资助（...1项目负责人曹云：复旦大学附属儿科医院新生儿科；Vibhuti Shah、Shoo K Lee：加拿大多伦多大学，加拿大Mount Sinai医院；王卫平：复旦大学100,40,20,10]2 资助者本研究方案获得美国中华医学基金会（China Medical Board,CMB）资助（项目编号：No.14-194）。3基于证据的质量改进（Evidence-based Practice for Improving Quality，EPIQ）方法介绍20世纪60~90年代，随着产前激素、新生儿呼吸支持等围生医学的进展，发达国家早产儿死亡率明显降低［1~5］。展开更多
原发性高血压是一种由遗传与环境因素共同导致的复杂疾病,具有高度的遗传异质性。自2007年首个高血压全基因组关联研究(Genome-wide association studies,GWAS)报道以来,许多GWAS相继开展。文章首先对2007年1月至2011年9月期间报道的24...原发性高血压是一种由遗传与环境因素共同导致的复杂疾病,具有高度的遗传异质性。自2007年首个高血压全基因组关联研究(Genome-wide association studies,GWAS)报道以来,许多GWAS相继开展。文章首先对2007年1月至2011年9月期间报道的24篇血压/高血压易感基因的GWAS按人种与染色体位置对其结果进行汇总,经统计位点rs17249754、rs1378942和rs11191548报道频数最多。其次介绍了GWAS方法学的研究进展,包括选择高质量的数量表型和选择多阶段研究设计来增加研究发现阳性关联的机会。统计分析方面,除强调了已经报道过的多重比较和重复(验证)研究等问题外,文章还介绍了通过Meta分析对GWAS数据进行深度发掘,并应用基因型填补法对缺失数据进行填补可以提高全基因组遗传标记的覆盖率的方法。尽管GWAS发现了许多我们未知的基因与疾病表型的关联,为了解高血压的发病机制提供了更多线索,但是目前GWAS发现的血压/高血压相关变异多为对人群血压的影响极其微弱的常见变异。因此今后的研究中可加强深度功能学研究对易感基因精细定位和外显子组测序技术的应用,结合GWAS的成果进行生物信息学通路分析和表观遗传学机制研究等,逐步揭示高血压的遗传机制。展开更多
文摘实现全基因组关联研究(Genome-wide association study,GWA)在数年前还是遗传学家们的梦想,如今它已经变成了现实。自2005年Science杂志报道了第一项有关年龄相关性(视网膜)黄斑变性全基因组关联研究研究以来,有关与复杂疾病的全基因组关联研究如雨后春笋般层出不穷。文中介绍了近两年来全基因组关联研究在复杂疾病研究领域内的主要发现、全基因组关联研究设计原理、遗传标记的选择、比较及相关商品信息。最后介绍了人类基因组拷贝数变异的研究进展,总结了人类全基因组关联研究所取得成就和存在的问题,并对全基因组关联研究未来的研究重点和要解决的问题进行了展望。
文摘Objective To develop a nationally acceptable blood pressure(BP)reference standards for the diagnosis and evaluation of hypertension in children and adolescents in China.Methods The current study was based on the data from eleven large-scale cross-sectional BP surveys in China's Mainland since 2001,the survey sites were representative of national geographical distribution including four municipalities(Beijing,Shanghai,Tianjin,Chongqing)and seven provinces(Hunan,Liaoning,Hebei,Zhejiang,Guangxi,Xinqiang and Guangdong).The surveys which met the following selection criteria were involved to form the reference population sample and pooled database:1)Subjects were Han nationality and their ages were from 3 to 18 years old;2)BP levels were measured by auscultation using standard sphygmomanometer and recorded as Korotkoff phase 1(SBP),Korotkoff phase 4(DBP-K4)and/or Korotkoff phase 5(DBP-K5);3)All surveyors were trained before investigations and standard quality control was implemented throughout the BP measuring process;4)Basic variables,except BPs,were at least included but not limited to age,sex,nationality,height and weight.Totally 112 227 subjects(56 912 males accounting for 50.7%)were enrolled in the reference population sample in this study.SPSS 13.0 software was used to do the descriptive statistical analysis.Centile curves for SBP,DBP-K4 and DBP-K5 were drawn by sex using LMS method.Z scores of Height and BMI were calculated based on the data from the Chinese National Survey on Constitution and Health(CNSCH)in schoolchildren in 2005 to evaluate the nutrition status and development level of the reference population.Results The reference population had an optimal representation of Chinese Han children and adolescents.The resulting curves provided specific cut off points based on age and sex for the diagnosis of high normal BP,hypertension and severe hypertension,respectively.Given the best approach for blood pressure measurement in children and adolescents remained controversial,especially on the choice of K4 or K5 for diastolic blood pressure.So in present study we showed DBP reference standards with K4 and K5,respectively,that is,two sets of SBP/DBP-K4 and SBP/DBP-K5 were developed for the flexible usage in practice.The proposed reference standards of SBP/DBP-K4 were similar to the US fourth report on the diagnosis,evaluation,and treatment of high blood pressure in children and adolescents,with only exception of the age groups of preschool children and late adolescence.Cut off points for hypertension using DBP-K5 were significantly lower than the US standards.Conclusions The proposed reference standards,which were firstly developed based on the most recently pooled national data and in line with the growth and development characteristics of Chinese children and adolescents,should help for the early screening,diagnosis and evaluation of hypertension in children and adolescents,and were also recommended to be used in national comparisons of prevalence of hypertension.
文摘1项目负责人曹云：复旦大学附属儿科医院新生儿科；Vibhuti Shah、Shoo K Lee：加拿大多伦多大学，加拿大Mount Sinai医院；王卫平：复旦大学100,40,20,10]2 资助者本研究方案获得美国中华医学基金会（China Medical Board,CMB）资助（项目编号：No.14-194）。3基于证据的质量改进（Evidence-based Practice for Improving Quality，EPIQ）方法介绍20世纪60~90年代，随着产前激素、新生儿呼吸支持等围生医学的进展，发达国家早产儿死亡率明显降低［1~5］。
文摘原发性高血压是一种由遗传与环境因素共同导致的复杂疾病,具有高度的遗传异质性。自2007年首个高血压全基因组关联研究(Genome-wide association studies,GWAS)报道以来,许多GWAS相继开展。文章首先对2007年1月至2011年9月期间报道的24篇血压/高血压易感基因的GWAS按人种与染色体位置对其结果进行汇总,经统计位点rs17249754、rs1378942和rs11191548报道频数最多。其次介绍了GWAS方法学的研究进展,包括选择高质量的数量表型和选择多阶段研究设计来增加研究发现阳性关联的机会。统计分析方面,除强调了已经报道过的多重比较和重复(验证)研究等问题外,文章还介绍了通过Meta分析对GWAS数据进行深度发掘,并应用基因型填补法对缺失数据进行填补可以提高全基因组遗传标记的覆盖率的方法。尽管GWAS发现了许多我们未知的基因与疾病表型的关联,为了解高血压的发病机制提供了更多线索,但是目前GWAS发现的血压/高血压相关变异多为对人群血压的影响极其微弱的常见变异。因此今后的研究中可加强深度功能学研究对易感基因精细定位和外显子组测序技术的应用,结合GWAS的成果进行生物信息学通路分析和表观遗传学机制研究等,逐步揭示高血压的遗传机制。
