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: 8233287
• 负责人: MARK A PEREIRA
• 金额: $ 59.11万
• 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/8233287
• 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）：尽管肥胖率较低，但东南亚人群的2型糖尿病率很高。这种“东南亚悖论”造成了极高的公共卫生和经济负担。尽管由世界卫生组织设定的东南亚特异性较低阈值定义肥胖症，但强调了这些族裔对T2D的特殊敏感性，但这些人群中过量糖尿病的基本生物学和环境原因尚不清楚。迄今为止，在欧洲人口中，T2D的全基因组关联研究已经完成，其他族裔群体没有。这些最近的遗传发现只会增加T2D的“东南亚悖论”，因为在欧洲人中发现的几种风险等位基因在亚洲人中的频率相对较低。我们的主要目的是确定居住在新加坡的中国人的T2D遗传易感性因素，那里的T2D患病率很高。该研究样本源自正在进行的新加坡中国卫生研究，这是一项基于人群的前瞻性队列，由63,257名成年男女在1993年至1998年组装，并不断遵循事件发病率和死亡率。自成立以来，NIH一直在支持新加坡中国卫生研究。新加坡国立大学的成本共享一直存在。所有生物样品都已经收集并准备好进行基因分型，并且在发生糖尿病病例的应计之前，所有环境因素均在基线时收集。因此，在以下方面，我们处于进行全基因组关联研究的独特位置：1）非常大的大小-6,132例和6,132个对照； 2）嵌套的病例对照设计 - 允许基因X环境相互作用； 3）我们目前对T2DM病因的独特，高风险人群； 4）新加坡基因组研究所和新加坡国立大学的大量成本分担，导致科学发现与货币成本的比例很高； 5）在两项外部亚洲队列研究中复制我们的发现。我们认为，本申请中提出的研究将推动该领域的前进，以了解许多亚洲人群中T2D的生物学和环境决定因素，并改善风险分层，以便可以确定最大风险的人以进行早期预防或治疗。尽管肥胖率较低，但东南亚与东南亚相关性在世界2型糖尿病的率最高，这是一种悖论，生物和环境决定因素仍不清楚。该项目的目的是在新加坡中国成年人的大型基于人群的研究中确定2型糖尿病的遗传和生活方式危险因素。这项研究具有巨大的潜力，可以提高我们对东南亚2型糖尿病风险的理解，从而改善预防努力。