Identification and Replication of Type 2 Diabetes Genes in Mexican Americans

墨西哥裔美国人 2 型糖尿病基因的鉴定和复制

• 批准号: 7789192
• 负责人: CRAIG L HANIS
• 金额: $ 51.29万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-20 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7789192
• 关键词: African American; Collaborations; County; DNA Resequencing; Data; Disease; Epidemic; Ethnic group; European; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Variation; Genome; Health; Human; Inherited; Investigation; Lead; Linkage Disequilibrium; Metabolic Pathway; Mexican Americans; Minority; Non-Insulin-Dependent Diabetes Mellitus; Phenotype; Play; Population; Population Group; Research; Research Design; Research Personnel; Resources; Risk; Role; Testing; Texas; Time; Variant; assault; blood glucose regulation; follow-up; genetic risk factor; genome wide association study; genome-wide; insight; prevent; programs; success; theories

DESCRIPTION (provided by applicant): With incredible rapidity the genome has become accessible. No fewer than 12 genome wide association studies have been performed for type 2 diabetes leading to the identification of at least 18 variants reproducibly associated in populations of recent European descent. Replication of specific variants in other population groups, however, has not been as consistent though the genes themselves often show associations. Interestingly, these 18 variants/genes do not seem to be related to each other through common metabolic pathways nor are most associated with previously understood connections to glucose homeostasis. Each merits intense investigation to develop deeper and broader understanding of their variation and function. Even with these 18 genes, we remain far short of a comprehensive understanding of the genetic underpinnings of type 2 diabetes in any population. The success in European populations indicates that extension to other ethnic groups will assuredly identify other genes. These efforts will be enhanced through appropriate combinations of data from multiple groups and careful testing within groups. The resources we have developed enabled an initial genome wide association study of type 2 diabetes among Mexican Americans and a second much larger such study with genetic markers currently being typed at the Center for Inherited Disease Research (CIDR) using the Affymetrix Genome-Wide Human SNP Array 6.0. The analyses and follow-up of these data in conjunction with a cadre of investigators bringing similar resources and analytic expertise for other ethnic groups will accelerate identification, replication and functional understanding of the genetic underpinnings of type 2 diabetes. We propose to become part of the NIDDK's "Multiethnic Study of Type 2 Diabetes Genes" (RFA-DK-09-004) and to: Aim 1: Comprehensively assess genetic variation in the vicinity of all SNPs reproducibly associated with type 2 with the risk for type 2 diabetes, its complications and related quantitative phenotypes in Mexican Americans from Starr County, Texas; Aim 2: Identify new genetic risk factors for type 2 diabetes in Mexican Americans, and Aim 3: Distinguish causal polymorphisms through deep resequencing and analyses that exploit network theory and evolutionary contexts. These studies will lead to substantial insights into the mechanisms leading to type 2 diabetes and move us much closer to the understanding required to slow its onset or prevent it. RELEVANCE: Type 2 diabetes is increasing at unprecedented rates in nearly all populations. Recent large scale studies have identified several genes that play a role in this. Using extensive data that we have developed on type 2 diabetes among Mexican Americans and joining our efforts with other groups will lead to the identification of other genes and, ultimately, strategies to slow the onset of type 2 diabetes and prevent it. Without such, we can only expect a continuing and increasing epidemic.

描述（由申请人提供）：基因组以令人难以置信的速度变得可访问。已经针对 2 型糖尿病进行了不少于 12 项全基因组关联研究，从而鉴定出至少 18 种与近代欧洲血统人群可重复相关的变异。然而，尽管基因本身经常表现出关联，但特定变异在其他人群中的复制并不那么一致。有趣的是，这 18 个变体/基因似乎并不通过常见的代谢途径相互关联，也与之前理解的葡萄糖稳态的联系最相关。每一个都值得深入研究，以更深入、更广泛地了解它们的变异和功能。即使有了这 18 个基因，我们仍然无法全面了解任何人群中 2 型糖尿病的遗传基础。在欧洲人群中的成功表明，扩展到其他种族群体肯定会识别出其他基因。这些努力将通过适当组合来自多个小组的数据以及小组内的仔细测试来加强。我们开发的资源支持了墨西哥裔美国人中 2 型糖尿病的初步全基因组关联研究，以及第二项规模更大的此类研究，其中遗传标记目前正在遗传性疾病研究中心 (CIDR) 使用 Affymetrix 全基因组人类 SNP 阵列 6.0 进行分型。对这些数据的分析和跟踪，以及为其他种族群体带来类似资源和分析专业知识的骨干研究人员的配合，将加速对 2 型糖尿病遗传基础的识别、复制和功能理解。我们提议成为 NIDDK 的“2 型糖尿病基因多种族研究”(RFA-DK-09-004) 的一部分，并： 目标 1：全面评估与 2 型糖尿病相关的所有 SNP 附近的遗传变异，以及来自德克萨斯州斯塔尔县的墨西哥裔美国人患 2 型糖尿病、其并发症和相关定量表型的风险；目标 2：确定墨西哥裔美国人 2 型糖尿病的新遗传风险因素，目标 3：通过利用网络理论和进化背景的深度重测序和分析来区分因果多态性。这些研究将带来对导致 2 型糖尿病的机制的深入见解，并使我们更接近于减缓或预防 2 型糖尿病的发病所需的理解。 相关性：2 型糖尿病在几乎所有人群中都在以前所未有的速度增长。最近的大规模研究已经确定了几个在其中发挥作用的基因。利用我们在墨西哥裔美国人中开发的关于 2 型糖尿病的大量数据，并与其他群体共同努力，将有助于识别其他基因，并最终找到减缓和预防 2 型糖尿病发病的策略。 如果没有这样的情况，我们只能预期疫情会持续且加剧。