Genetic and Environmental Determinants of Type 2 Diabetes in Chinese Singaporeans

新加坡华人 2 型糖尿病的遗传和环境决定因素

• 批准号: 8033084
• 负责人: MARK A PEREIRA
• 金额: $ 61.15万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8033084
• 关键词: Adult; Age; Alleles; Asians; Biological; Body mass index; Caucasians; Caucasoid Race; Cereals; Characteristics; Chinese People; Cohort Studies; Cost Sharing; DNA Resequencing; Data; Diabetes Mellitus; Dietary Practices; Economic Burden; Environment; Environmental Risk Factor; Ethnic group; Etiology; European; Fatty acid glycerol esters; Frequencies; Future; Gender; Gene Frequency; Genes; Genetic; Genetic Epistasis; Genetic Predisposition to Disease; Genome; Genotype; Health; High Prevalence; Human Genome; Institutes; International; Japanese American; Life; Life Style; Logistic Regressions; Maps; Meat; Modeling; Modification; Morbidity - disease rate; National Cancer Institute; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Physical activity; Population; Population Sizes; Positioning Attribute; Predisposition; Prevention; Public Health; Publishing; Research Design; Risk; Risk Factors; Sampling; Sampling Studies; Scanning; Singapore; Single Nucleotide Polymorphism; Southeastern Asia; Staging; Stratification; Testing; Time; United States National Institutes of Health; Universities; Variant; Woman; World Health Organization; base; burden of illness; case control; cohort; cost; design; diabetes risk; follow-up; fruits and vegetables; genome wide association study; global health; health economics; high risk; improved; men; mortality; pandemic disease; population based; prospective; research study; southeast Asian; trend

DESCRIPTION (provided by applicant): Southeast Asian populations have high rates of type 2 diabetes (T2D) despite low rates of obesity. This "Southeast Asian Paradox" has caused an extremely high public health and economic burden. While Southeast Asian-specific lower thresholds for defining obesity, set by the World Health Organization, underscore the particular susceptibility of these ethnic groups to T2D, the underlying biological and environmental causes for the excess diabetes in these populations are unknown. To date, genome-wide association studies of T2D have been completed in European populations, with none in other ethnic groups. These recent genetic findings only add to a "Southeast Asian Paradox" of T2D because several of the risk alleles found in Europeans have relatively low frequencies in the Asians. Our main aim is the identification of genetic susceptibility factors for T2D in Chinese living in Singapore, where there is a high prevalence of T2D. The study samples are derived from the ongoing Singapore Chinese Health Study, a population-based prospective cohort of 63,257 adult men and women assembled during 1993-1998 and continuously followed to date for incident morbidity and mortality. The NIH has been supporting the Singapore Chinese Health Study since its inception. There has been and continues to be significant cost- sharing by the National University of Singapore. All biological samples have already been collected and are ready for genotyping, and all environmental factors have been collected at baseline prior to the accrual of incident diabetes cases. Thus, we are in a unique position of conducting a genome-wide association study like none other to date in the following respects: 1) Very large size - 6,132 cases and 6,132 controls; 2) Nested case-control design - allowing for gene x environment interactions; 3) Unique, high risk population for which we currently have a weak understanding of T2DM etiology; 4) Extensive cost-sharing by the Genome Institute of Singapore and National University of Singapore, resulting in a high ratio of scientific discovery to monetary cost; and 5) Replication of our findings in two external Asian cohort studies. We believe the study proposed in this application will move the field forward in understanding the biological and environmental determinants of T2D in many Asian populations, and improve risk stratification so that those at greatest risk can be identified for early prevention or treatment. PUBLIC HEALTH RELEVANCE Southeast Asians have among the world's highest rates of type 2 diabetes despite low rates of obesity, a paradox for which the biological and environmental determinants remain unclear. The objective of this project is to identify the genetic and lifestyle risk factors for type 2 diabetes in a large population-based study of Singaporean Chinese adults. The study has tremendous potential to improve our understanding of type 2 diabetes risk in Southeast Asians, leading to improved prevention efforts.

描述（由申请人提供）：尽管东南亚人口的肥胖率较低，但 2 型糖尿病 (T2D) 的发病率较高。这种“东南亚悖论”造成了极高的公共卫生和经济负担。虽然世界卫生组织设定的东南亚特定的肥胖定义较低阈值强调了这些种族群体对 T2D 的特殊易感性，但这些人群中糖尿病过多的潜在生物学和环境原因尚不清楚。迄今为止，T2D 的全基因组关联研究已在欧洲人群中完成，而在其他种族群体中尚未完成。这些最近的基因发现只会增加 T2D 的“东南亚悖论”，因为在欧洲人中发现的几个风险等位基因在亚洲人中出现的频率相对较低。我们的主要目的是确定居住在新加坡的中国人中 T2D 的遗传易感因素，新加坡的 T2D 患病率很高。研究样本来自正在进行的新加坡华人健康研究，该研究是一个以人群为基础的前瞻性队列，在 1993 年至 1998 年间收集了 63,257 名成年男性和女性，并持续跟踪迄今为止的事件发病率和死亡率。自新加坡华人健康研究成立以来，美国国立卫生研究院一直支持该研究。新加坡国立大学已经并将继续承担大量费用。所有生物样本均已收集完毕并准备好进行基因分型，所有环境因素均已在糖尿病病例发生之前收集到基线。因此，我们在开展全基因组关联研究方面处于独特的地位，在以下方面是迄今为止独一无二的：1) 规模非常大——6,132 个病例和 6,132 个对照； 2）嵌套病例对照设计——允许基因x环境相互作用； 3）目前我们对T2DM病因了解甚少的独特高危人群； 4）新加坡基因组研究所和新加坡国立大学广泛分摊成本，导致科学发现与货币成本的比率很高； 5) 在两项外部亚洲队列研究中复制了我们的研究结果。我们相信，本申请中提出的研究将推动该领域进一步了解许多亚洲人群中 T2D 的生物和环境决定因素，并改善风险分层，以便识别出风险最大的人群，以便进行早期预防或治疗。公共卫生相关性 尽管肥胖率较低，但东南亚地区的 2 型糖尿病发病率仍然是世界上最高的，而造成这一悖论的生物学和环境决定因素仍不清楚。该项目的目标是通过一项针对新加坡华裔成年人的大型人群研究来确定 2 型糖尿病的遗传和生活方式风险因素。这项研究具有巨大的潜力，可以提高我们对东南亚人 2 型糖尿病风险的了解，从而改善预防工作。