Common Genetic Variation and Quantitative Diabetes Traits

常见的遗传变异和定量糖尿病特征

• 批准号: 8705791
• 负责人: JAMES B MEIGS
• 金额: $ 19.73万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8705791
• 关键词: Accounting; Affect; African American; Alleles; Architecture; Asians; Back; Beta Cell; Body Weight Changes; Caring; Cell physiology; Chromosome Mapping; Clinical; Collection; Complex; Coupled; Data; Diabetes Mellitus; Diabetes prevention; Diagnosis; Disease; Environment; Ethnic Origin; Ethnic group; Etiology; European; Evolution; Functional disorder; Funding; General Population; Genes; Genetic; Genetic Research; Genetic Variation; Genomics; Genotype; Glucose; Glycosylated Hemoglobin; Glycosylated hemoglobin A; Goals; Health; Hispanics; Individual; Insulin; Insulin Resistance; Knowledge; Link; Maps; Measures; Meta-Analysis; Metabolic; Metabolic Pathway; Minority Groups; Mutation; National Institute of Diabetes and Digestive and Kidney Diseases; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Pathway interactions; Phenotype; Physiological; Physiology; Population; Prevention; Prevention strategy; Public Health; Quantitative Trait Loci; Resources; Risk; Sampling; Sampling Studies; Staging; Support Groups; Target Populations; Testing; Time; To specify; Translations; Variant; Work; base; clinical application; diabetes mellitus genetics; diabetes risk; fasting glucose; follow-up; gene discovery; gene environment interaction; gene interaction; genetic resource; genome wide association study; improved; next generation sequencing; non-diabetic; novel; novel strategies; permissiveness; population based; trait; Accounting; Affect; African American; Alleles; Architecture; Asians; Back; Beta Cell; Body Weight Changes; Caring; Cell physiology; Chromosome Mapping; Clinical; Collection; Complex; Coupled; Data; Diabetes Mellitus; Diabetes prevention; Diagnosis; Disease; Environment; Ethnic Origin; Ethnic group; Etiology; European; Evolution; Functional disorder; Funding; General Population; Genes; Genetic; Genetic Research; Genetic Variation; Genomics; Genotype; Glucose; Glycosylated Hemoglobin; Glycosylated hemoglobin A; Goals; Health; Hispanics; Individual; Insulin; Insulin Resistance; Knowledge; Link; Maps; Measures; Meta-Analysis; Metabolic; Metabolic Pathway; Minority Groups; Mutation; National Institute of Diabetes and Digestive and Kidney Diseases; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Pathway interactions; Phenotype; Physiological; Physiology; Population; Prevention; Prevention strategy; Public Health; Quantitative Trait Loci; Resources; Risk; Sampling; Sampling Studies; Staging; Support Groups; Target Populations; Testing; Time; To specify; Translations; Variant; Work; base; clinical application; diabetes mellitus genetics; diabetes risk; fasting glucose; follow-up; gene discovery; gene environment interaction; gene interaction; genetic resource; genome wide association study; improved; next generation sequencing; non-diabetic; novel; novel strategies; permissiveness; population based; trait

DESCRIPTION (provided by applicant): The goal of this R01DK78616 renewal is to identify new type 2 diabetes (T2D) quantitative trait (QT) loci in a large trans-four-ethnic sample (N~103,000: ~26K African American, ~46K European, ~14K Hispanic and ~17K Asian) using staged genome-wide association studies with meta-analysis (GWAS-MA). In the trans- ethnic sample we will further test gene-environment and gene-gene interactions and gene pathways, and in longitudinal data, test candidate loci for physiological effects and for T2D prediction. Our links with other NIDDK studies offer immediate follow-up for next-generation sequencing (U01 DK085526) and trials of clinical application of genetics for T2D prevention (R21 DK084527). The significant recent, dramatic increase in T2D in the U.S., especially in minority groups, is an escalating clinical and public health challenge. Variation in genetic background coupled with increasing obesity accounts for rising T2D in the U.S.. In people of European ancestry, large-scale GWAS-MA have successfully outlined T2D common genetic architecture, with consortia studies led by our group and our collaborators recently contributing >50 new T2D risk or T2D QT loci. Large trans-ethnic GWAS-MA is a key next step in T2D gene discovery. Specific Aims are to: 1) Identify novel T2D QT-associated variants using GWAS-MA in large, non-diabetic, trans-ethnic samples. We hypothesize that: a) staged GWAS-MA of T2D QTs in a large non-diabetic African American sample will identify novel loci associated with T2D physiology and T2D risk and b) joining the African American T2D QT GWAS-MA with three other groups for a large trans-four-ethnic T2D QT GWAS-MA will identify additional loci; 2) Use the large trans-ethnic sample to find more loci, fine map, and suggest mechanism by tests of gene-environment, gene-gene and gene pathway analyses, specifically, accounting for SNP x BMI, weight change, ethnicity and other interactors; and 3) Use longitudinal population-based data to iluminate the evolution of T2D physiology over time, define the allelic spectrum of risk in U.S. ethnic groups, and test if novel T2D-related variants aid T2D risk prediction. The trans-four-ethnic GWAS-MA will provide an unparalleled resource for genetic discovery, studies of interactions and pathways hypothesized to underlie T2D and its related QTs, and help better define the value of T2D genetics for physiological targeting, population prediction and personalized prevention to improve health in minority and non-minority groups the U.S..

DESCRIPTION (provided by applicant): The goal of this R01DK78616 renewal is to identify new type 2 diabetes (T2D) quantitative trait (QT) loci in a large trans-four-ethnic sample (N~103,000: ~26K African American, ~46K European, ~14K Hispanic and ~17K Asian) using staged genome-wide association studies with meta-analysis （GWAS-MA）。在跨民族样本中，我们将进一步测试基因环境和基因 - 基因相互作用和基因途径，以及在纵向数据中，测试候选基因座的生理效应和T2D预测。我们与其他NIDDK研究的联系提供了下一代测序（U01 DK085526）的立即随访以及遗传学在T2D预防中的临床应用试验（R21 DK084527）。美国T2D最近的重大增长，尤其是在少数群体中，临床和公共卫生挑战率不断提高。遗传背景的差异以及肥胖的增加构成了美国T2D的上升。大型跨种族GWAS-MA是T2D基因发现的关键下一步。具体目的是：1）使用GWAS-MA在大型非糖尿病，跨种族样本中鉴定新型T2D QT相关的变体。我们假设：a）在大型非糖尿病的非裔美国人样本中登上T2D QT的GWAS-MA，将确定与T2D生理学和T2D风险相关的新颖的基因座，以及b）加入非裔美国人T2D QT GWAS-MA，与其他三个小组与其他三个小组一起为大型Trans-Four T2D QT QT GWAS-GWAS-GWAS-MA确定其他型号。 2）使用大型的跨种族样本查找更多基因座，精细的地图和通过基因环境，基因基因和基因途径分析的测试，特别是考虑到SNP X BMI，体重变化，种族和其他相互作用的人； 3）使用基于纵向人群的数据随着时间的流逝而缩放T2D生理学的演变，定义美国族裔的风险等位基因谱，并测试新型与T2D相关的变体是否有助于T2D风险预测。跨四个族裔GWAS-MA将为遗传发现，对T2D基础及其相关QTS的相互作用和途径的研究提供无与伦比的资源，并有助于更好地定义T2D遗传学对生理靶向，人群预测和个性化预防的T2D遗传学价值，以改善少数群体和非中等群体的健康。