Identifying Genes for Type 2 Diabetes: FUSION

识别 2 型糖尿病基因：FUSION

• 批准号: 8105440
• 负责人: MICHAEL L BOEHNKE
• 金额: $ 125.26万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8105440
• 关键词: 20 year old; 20q; Adipose tissue; Affect; Age; American; Behavioral; Biological; Biological Assay; Candidate Disease Gene; Cell Line; Cell Lineage; Chromosomes; Clinical Data; Collaborations; Complex; DNA; DNA Resequencing; Data; Diabetes Mellitus; Disease; Epidemic; Etiology; European; Expenditure; Family; Fatty acid glycerol esters; Finland; Frequencies; Funding; Generations; Genes; Genetic; Genomics; Genotype; Germany; Glucose; Goals; Health Care Costs; Height; Hepatocyte; Hereditary Disease; IL6 gene; Incidence; Individual; Investigation; Joints; Leadership; Learning; Letters; Lipids; Los Angeles; Maps; Medical; Meta-Analysis; Methods; Mitochondria; Molecular Genetics; Morbidity - disease rate; Muscle; National Human Genome Research Institute; Non-Insulin-Dependent Diabetes Mellitus; Norway; Participant; Pharmacotherapy; Phenotype; Population; Predictive Value; Predisposition; Prevalence; Prevention; Preventive; Public Health; Quantitative Trait Loci; Rare Diseases; Reporting; Research Design; Risk; Sampling; Siblings; Signal Transduction; Skin; Specimen; Statistical Study; Study Subject; TCF7L2 gene; Therapeutic; Tissue Microarray; Tissue Sample; Tissues; United States; United States National Institutes of Health; Variant; Work; aged; base; diabetes risk; fasting glucose; follow-up; functional genomics; genetic variant; genome wide association study; genome-wide; improved; induced pluripotent stem cell; islet; mRNA Expression; mortality; novel; precursor cell; resistin; sex; socioeconomics; success; therapy development; trait

Type 2 diabetes (T2D) is a major cause of morbidity and mortality in the USA and worldwide. While disease prevalence varies with age, sex, and population, it is estimated that in 2005, 20.6 million Americans aged 20 years or older and 10.3 million Americans aged 60 years or older suffered from T2D. Similar rates of T2D have been observed in Finland. The incidence and prevalence of T2D are increasing in the USA and worldwide. In the USA alone, it is estimated that medical expenditures due to diabetes totaled $132 billion in 2002, ~10% of all USA health care costs. The increasing number of younger T2D cases amplifies the socioeconomic impact of T2D and increases the urgency with which we must act to identify its causes and new treatments. There is substantial evidence of a genetic component in the etiology of T2D and T2D-related quantitative traits (QTs). The goal of the Finland-United States Investigation of NIDDM Genetics (FUSION) study is to identify genetic variants that predispose to T2D and that are responsible for variability in T2D-related QTs. Improved understanding of the genetic basis of T2D and related QTs has the potential to reduce the impact of the current T2D epidemic by supporting identification of novel drugs and therapies, enabling better targeting of preventive and therapeutic approaches, and providing more accurate T2D risk prediction. In this proposal, we seek to build on our successes of the last five years, particularly the initial findings of our genome-wide association studies of T2D and related QTs. Specifically, we will (1) increase substantially our available sample of well-phenotyped study subjects, (2) obtain tissue samples (fat, muscle, skin) and carry out functional assays on an extensively studied subset of our study subjects using these tissues and the wider array of tissues made possible by the directed differentiation of induced pluripotent stem cell (iPS) lines into precursor cell lineages towards but not limited to the generation of islet-like and hepatocyte-like tissues, (3) continue and expand on our current genome-wide analyses to identify additional T2D and T2D- related-QT loci by using our existing Finnish samples, samples newly-obtained during this project period, and continued joint and/or meta-analysis with collaborators, and (4) fine map and identify predisposing variants in the T2D and QT loci we have discovered or will discover, assess the allelic spectrum of relevant variants, and assess the predictive power of identified variants. These efforts will contribute to improved understanding of the etiology of T2D, and have the potential to point the way to novel methods of treatment and prevention. Methods developed and lessons learned in this study will be useful in the study of other complex genetic diseases.

2型糖尿病（T2D）是美国和全球发病率和死亡率的主要原因。尽管疾病患病率随着年龄，性别和人口而异，但据估计，在2005年，2060万名20岁以上的美国人和6030万名60岁或60岁以上的美国人患有T2D。在芬兰已经观察到类似的T2D速率。在美国和全球，T2D的发病率和患病率正在增加。仅在美国，据估计，2002年由于糖尿病造成的医疗支出总计1,320亿美元，占美国医疗保健费用的10％。越来越多的年轻T2D案例扩大了T2D的社会经济影响，并增加了我们必须采取行动以确定其原因和新治疗的紧迫性。在T2D和T2D相关的定量性状（QTS）的病因学中，有大量证据表明遗传成分。 NIDDM遗传学研究（Fusion）研究的目的是确定易于T2D的遗传变异，并导致T2D相关QT的变异性。对T2D和相关QT的遗传基础的了解得以提高，通过支持鉴定新药物和疗法的鉴定，可以更好地靶向预防和治疗方法，并提供更准确的T2D风险预测，从而减少当前T2D流行病的影响。在这一建议中，我们试图以过去五年的成功为基础，尤其是我们全基因组协会研究T2D和相关QT的最初发现。 Specifically, we will (1) increase substantially our available sample of well-phenotyped study subjects, (2) obtain tissue samples (fat, muscle, skin) and carry out functional assays on an extensively studied subset of our study subjects using these tissues and the wider array of tissues made possible by the directed differentiation of induced pluripotent stem cell (iPS) lines into precursor cell lineages towards but not limited to the generation of islet-like （3）（3）通过使用我们现有的芬兰样本，在这个项目期间新近观察到的样本，并继续关节和/或元分析，与合作者和（4）发现了predisspspiptions prediss prediant ofissp，prediant ofisspsptimpspector and（4）prediss prediss prediss prediant ofisspsptightiant of Prediatiant ofisspspepts，（3）继续与合作者和元分析质量图，（4）prediss prediss prediss prediant of the22评估相关变体的等位基因谱，并评估已识别变体的预测能力。这些努力将有助于改善对T2D病因的理解，并有可能为新颖的治疗和预防方法指出道路。开发的方法和本研究中学的教训将在研究其他复杂遗传疾病的研究中很有用。