Genetics of Metabolic Syndrome in an Island Population

岛屿人群代谢综合征的遗传学

• 批准号: 7272049
• 负责人: Ranjan Deka
• 金额: $ 51.02万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7272049
• 关键词: Accounting; Adult; Age-Years; American; Architecture; Arts; Back; Biochemical; Biological; Blood Pressure; Blood specimen; Carbohydrates; Cardiovascular Diseases; Chromosome Mapping; Classification; Clinical; Clinical Data; Collection; Complex; Condition; Croatia; DNA; Data; Developed Countries; Developing Countries; Development; Disease; Dyslipidemias; Environment; Epidemic; Exhibits; Family; Family Sizes; Genealogy; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Variation; Genome; Glucose; Goals; High Blood Pressure; High Prevalence; Individual; Insulin; Intervention; Investigation; Island; Knowledge; Life Style; Lipids; Location; Measures; Metabolic syndrome; Morbidity - disease rate; Non-Insulin-Dependent Diabetes Mellitus; Nucleotides; Numbers; Obesity; Phenotype; Population; Population Research; Population Study; Predisposition; Public Health; Recording of previous events; Records; Recruitment Activity; Research; Research Personnel; Risk; Risk Factors; Sampling; Score; Syndrome; Testing; Variant; base; community living; density; design; genetic analysis; genetic epidemiology; genetic linkage analysis; genetic pedigree; genetic variant; genome wide association study; genome-wide linkage; impaired glucose tolerance; indexing; mortality; prevent; trait; transmission process

DESCRIPTION (provided by applicant): Metabolic syndrome (MetS), a constellation of risk factors associated with development of cardiovascular disease and Type 2 diabetes, has reached epidemic proportions in western industrialized nations. About 47 million Americans have MetS. Consequently, it has enormous impact on public health. The hallmark of MetS is a co-occurrence of obesity, dyslipidemia, carbohydrate intolerance and high blood pressure. Familial aggregation of the individual components and the composite MetS trait suggests involvement of genetic factors. However, our knowledge concerning the genetic factors underlying MetS remains largely incomplete. We propose to undertake a thorough investigation on epidemiology and genetics of MetS in an isolated population from the island of Hvar in the eastern Adriatic coast of Croatia. The value of isolated population in complex disease gene mapping has been widely documented. The study population has a high prevalence of MetS, is ethnically relevant to the general US population, with its distinct evolutionary history of recent founding by small number of Slavic founders, geographic isolation, environmental homogeneity, extended family sizes provides a unique opportunity to understand the genetics of MetS. We propose to (1) recruit 1200 individuals above 20 years of age from five villages of Hvar, collect demographic, environmental, life-style, phenotypic, relevant clinical data, and blood samples for analysis of biochemical traits and DNA; (2) conduct appropriate analyses to estimate the effects of genetic contribution to the variability of MetS as a composite trait and its constituent phenotypes; (3) conduct a whole genome scan using a panel of densely spaced, 10K, SNP markers for linkage analysis; (4) followed by pedigree-based association studies using a 'positional candidate' approach in the regions of significant linkage for identification of genetic variants associated with MetS. The study has enormous public health importance and its scientific merit is substantial with the potential of understanding the genetic etiology of MetS. We will study an ideal population for this research; our use of dense SNP markers for linkage and association is a state-of-the-art approach and has enormous promise for identifying loci and gene variants underlying MetS.

描述(申请人提供)：代谢综合征(METS)，一系列与心血管疾病和2型糖尿病的发展相关的危险因素，在西方工业化国家已经达到流行的程度。大约有4700万美国人有大都会医院。因此，它对公众健康有巨大的影响。METS的特点是肥胖、血脂异常、碳水化合物不耐受和高血压并存。个体成分和复合蛋氨酸性状的家族聚集性表明遗传因素参与其中。然而，我们对METS背后的遗传因素的了解在很大程度上仍然不完整。 我们建议在克罗地亚东部亚得里亚海沿岸的赫瓦岛上的一个孤立人口中进行一次彻底的甲型肝炎流行病学和遗传学调查。隔离群体在复杂疾病基因定位中的价值已经被广泛地记录下来。研究人群有很高的METS患病率，在种族上与普通美国人口相关，其独特的进化史是由少数斯拉夫创始人最近创立的，地理上的隔离，环境的同质性，扩大的家庭规模为了解METS的遗传学提供了独特的机会。 我们建议(1)从Hvar的5个村庄招募1200名20岁以上的个体，收集人口、环境、生活方式、表型、相关临床数据和血液样本，用于生化性状和DNA分析；(2)进行适当的分析，以估计遗传对METS作为一个综合性状及其组成表型的变异性的影响；(3)使用一组密集分布的10K SNP标记进行全基因组扫描，进行连锁分析；(4)在显著连锁的区域使用‘位置候选’方法进行基于系谱的关联研究，以识别与METS相关的遗传变异。 这项研究具有巨大的公共卫生重要性，它的科学价值是实质性的，有可能理解METS的遗传病因。我们将为这项研究研究一个理想的群体；我们使用密集的SNP标记进行连锁和关联是一种最先进的方法，在识别MET的基因座和基因变异方面具有巨大的前景。