Genetics of Type 2 Diabetes in Indian Populations: US-India Collaboration Project

印度人群 2 型糖尿病的遗传学：美印合作项目

• 批准号: 9258433
• 负责人: RAVINDRANATH DUGGIRALA
• 金额: $ 16.53万
• 依托单位: UNIVERSITY OF TEXAS RIO GRANDE VALLEY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-08 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9258433
• 关键词: Affect; African American; Alcohol consumption; American; Anxiety; Architecture; Behavioral; Cardiovascular Diseases; Castes; Clinical Data; Collaborations; Comorbidity; Complex; Data; Data Set; Development; Diabetes Mellitus; Diet; Dietary intake; Disease; Dyslipidemias; Enrollment; Environment; Environmental Risk Factor; Epidemiology; Ethnic group; European; Exhibits; Family; Family Study; Foundations; Frequencies; Functional disorder; Funding Opportunities; Genes; Genetic; Genetic Determinism; Genetic Predisposition to Disease; Genetic Variation; Genotype; Health; Healthcare; Heritability; Immigrant; India; Individual; Institution; Joints; Knowledge; Linguistics; Medical Research; Mental Depression; Metabolic; Metabolic syndrome; Mexican Americans; Molecular; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Pathogenesis; Pathway interactions; Phenotype; Physical activity; Population; Population Study; Predisposition; Prevalence; Public Health; Recruitment Activity; Request for Applications; Research; Resources; Role; Rural; Sampling; Single Nucleotide Polymorphism; Socioeconomic Status; South Asian; Susceptibility Gene; Targeted Resequencing; Technology; United States; United States National Institutes of Health; Variant; base; cigarette smoking; comparative; design; epidemiology study; ethnic minority population; experience; genetic analysis; genetic pedigree; genetic variant; genome wide association study; health disparity; interest; member; novel; population health; proband; psychologic; public health relevance; rare variant; response; social; trait

 DESCRIPTION (provided by applicant): Type 2 diabetes (T2D) has become a major public health issue in both India and the United States (US). In consideration of its epidemiological burden and the related population health disparities, there have been continued efforts to understand the factors underlying its phenotypic expression. Given its significance as a binational healthcare problem, the National Institutes of Health (NIH RFA-DK-14-006) and the Indian Council: of Medical Research (ICMR) have come together to announce funding opportunities to support Binational Collaborative Research Partnerships (CRPs) on diabetes research. There is a paucity of genetic epidemiologic investigations of T2D in India. In response to this initiative, we have formed a new CRP involving two US institutions and three Indian institutions to evaluate genetic determinants of T2D among four endogamous ethnic groups (EEGs) using pedigree-based data sets from two North and two South Indian states. The specific aims of this joint experimental/developmental proposal are detailed below, which will be accomplished by Indian or US partners or both of them jointly. As part of Aim 1a, we will recruit 1500 individuals from ~60 large families from three genetically and culturally diverse EEGs from the states of Rajasthan (Agarwal EEG), Tamil Nadu (Chettiar EEG), and Andhra Pradesh (Reddy EEG); 500 individuals from 20 large families (25 members per family) from each EEG will be ascertained on T2D probands. The family- phenotypic- and genotypic data, from a Sikh Khatri EEG from the state of Punjab are already collected and will be available for this study. Clinical data related to T2D and information on environmental covariates (e.g., diet and physical activity) will be collected (Aim 1b). Through Aims 2a and 2b, several genetic analyses will be conducted such as determination of heritability of T2D, and comparative analyses will be performed between Indian populations and the US multi-ethnic populations including European Americans, African Americans, and Mexican Americans as they relate to T2D pathogenesis and pathophysiology. Most importantly, we will pursue genetic regions harboring 8 T2D susceptibility loci previously identified in South Asians including the Punjabi Sikh population by performing targeted resequencing, using samples (N=336) from the Punjabi Sikh EEG families and assess associations between T2D and rare and low frequency variants detected through sequencing (Aim 3a). The best associated ~200 genetic variants with T2D will be confirmed in an additional sample of 4,000 Sikh individuals (Aim 3b). As part of Aim 4, the best associated ~100 SNPs from Aim 3b together with ~100 genetic variants representing the established T2D susceptibility loci from non-Indian populations will be confirmed in the three EEGs enrolled as part of Aim 1. Maximizing the expertise, research experience, and resources of the US and Indian collaborative teams, our study will lay a strong foundation to critically examine genetic, social and cultural differences among the Indian EEGs. To our knowledge, this is the first Indo-US collaborative effort to apply pedigree-based design and sequencing technologies to identify novel causal genes and molecular pathways associated with T2D.

 描述（由适用提供）：2型糖尿病（T2D）已成为印度和美国（美国）的主要公共卫生问题。考虑到其流行病学烧伤和相关的人口健康分布，一直在继续努力理解其表型表达的因素。鉴于其作为二元医疗问题的重要性，美国国立卫生研究院（NIH）RFA-DK-14-006）和印度理事会：医学研究（ICMR）齐聚一堂，宣布了支持Binational合作研究合作伙伴关系（CRP）的资金机会。印度T2D的遗传流行病学研究很少。为了回应这一倡议，我们使用来自两个北部和两个南印度州的两个基于血统的数据集在四个内婚族裔群体（EEG）中评估T2D的遗传决定师（EEG）的新CRP。下面详细介绍了该联合实验/发展建议的具体目的，这将由印度或美国合作伙伴或两者共同完成。作为AIM 1A的一部分，我们将招募来自拉贾斯坦邦（Agarwal EEG），泰米尔纳德邦（Chettiar EEG）和Andhra Pradesh（Reddy EEG）的三个普遍和文化多样化的脑电图的约60个大家庭的1500个人； T2D概率将确定来自每个脑电图的20个大家庭（每个家庭25个成员）的500个人（每个家庭25个成员）。来自旁遮普邦的锡克教khatri EEG的家庭表型和基因型数据已经收集，将用于本研究。将收集与T2D和环境协变量信息有关的临床数据（例如，饮食和体育锻炼）（AIM 1B）。通过AIM 2A和2B，将进行一些遗传分析，例如确定T2D的遗传力，并将在印度人口与包括欧洲裔美国人，非裔美国人和墨西哥裔美国人在内的印度人口之间进行比较分析，因为它们与T2D病原体和病理生理学有关。最重要的是，我们将使用先前在南亚人（包括旁遮普锡克教人口）中确定的8 t2d易感基因座的遗传区域，使用针对性的重新取证，使用旁遮普锡克教锡克教案的样本（n = 336），来自T2D和稀有和低频率变种的旁遮普锡克教锡克教均来自旁遮普锡的锡克教家庭和评估协会。最佳相关的〜200个与T2D的遗传变异将在4,000个锡克教个体的其他样本中得到证实（AIM 3B）。作为目标4的一部分，AIM 3B的最佳〜100个SNP以及约有100个遗传变异体，代表了非印度人群的T2D易感性地方，将在AIM 1的三个EEG中得到确认。最大化美国和印度协作团队的专业知识，研究经验和资源，我们的研究将在Indians中最大化，我们的研究将在印度的范围内进行强大的基础和社会化的基础。据我们所知，这是使用基于血统的设计和测序技术来识别新型因果基因和与T2D相关的分子途径的第一项Indo-US协作努力。