Genome-wide-association Studies in Chagas Cardiomyopathy

恰加斯心肌病的全基因组关联研究

• 批准号: 10115586
• 负责人: ALEXANDRE DA COSTA PEREIRA
• 金额: $ 15.81万
• 依托单位: FUNDACAO FACULDADE DE MEDICINA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10115586
• 关键词: Acute; Address; Area; Arrhythmia; Benznidazole; Cardiac; Cardiomyopathies; Cause of Death; Cessation of life; Chagas Disease; Child; Chronic; Clinical; Cohort Studies; Country; DNA; Data; Deterioration; Development; Dilatation - action; Disease; Disease Progression; Disease susceptibility; Emerging Communicable Diseases; Enrollment; Failure; Family; Family member; Future; Genes; Genetic; Genetic Predisposition to Disease; Genetic Variation; Genetic study; Genotype; Heart; Heart Diseases; Heart failure; Heritability; Immigrant; Individual; Infection; Insect Vectors; Institutes; Investigation; Knowledge; Latin America; Latin American; Meta-Analysis; Minor; Mothers; Nuclear Family; Organ; Parasites; Patients; Politics; Predisposition; Prognostic Marker; Research; Role; Sampling; Stroke; Syndrome; Testing; Thromboembolism; Tropical Medicine; Trypanosoma cruzi; Ventricular; base; biomarker discovery; blood product; cardiogenesis; chagasic cardiomyopathy; cohort; disability-adjusted life years; end stage disease; experimental study; genetic approach; genome wide association study; genome-wide; heart damage; heart function; infection risk; mortality; premature; rare variant; recruit; sample collection; seropositive; tool; transmission process; working group

PROJECT SUMMARY Chagas cardiomyopathy is still a leading cause of death in Latin American countries. It is also an emerging infectious disease in the US, estimated to have approximately 300,000 individuals with Chagas disease living within its borders. One of the most important and still unanswered questions in the disease is why only 30% of infected individuals develop chronic forms of end-stage cardiomyopathy. Here we hypothesize that genetic susceptibility is paramount and modulates end-stage disease development. For testing this hypothesis we will use a genetics approach based on the investigation of common genetic variation that may associate with disease development. In parallel, we will build the tools to also investigate whether rare genetic variations also have a role in disease susceptibility. This enterprise will be possible thanks to the team of several different Brazilian groups around this project. We will harness GWAS data already collected and generated by the REDS-II Study, the Bambui Study, and the Heart Institute Heart Failure Cohort Study. In addition, we will generate new large-scale genotype data from the SaMi-Trop Cohort. Taken together, our efforts will result on a more than 10-fold increase in the number of available individuals with Chagas disease that can be analyzed using a GWAS approach. Specifically, we propose to address this problem through the following specific aims: 1. Recruit 1,000 new individuals with the indeterminate form at the Montes Claros, MG region and conduct genome-wide genotyping experiments in 2,000 samples available from the SaMi-Trop cohort, the new indeterminate form group, and approximately 1,000 un-genotyped samples from the Brazilian Consortium for Genetics of Chagas Cardiomyopathy; 2. Conduct a meta-analysis of the different GWAS studies taking part in this initiative; 3. Ascertain and enroll T. cruzi infected individuals from the same nuclear families for the conduct of Chagas cardiomyopathy heritability and future sequencing studies.

项目摘要 Chagas心肌病仍然是拉丁美洲国家死亡的主要原因。这也是一个新兴的 美国的传染病，估计有大约30万人患有chagas病的人 在其边界内。疾病中最重要，最重要的问题之一是为什么只有30％ 受感染的个体发展为终末期心肌病的慢性形式。在这里，我们假设该遗传 敏感性至关重要，调节末期疾病的发展。为了检验这个假设，我们将 根据对常见遗传变异的研究，使用遗传学方法 疾病发展。同时，我们将构建工具，还可以研究罕见的遗传变异 在疾病易感性中起作用。 由于该项目围绕该项目的几个不同的巴西团体组成的团队，该企业将有可能。我们 将利用Reds-II研究，BAMBUI研究和已收集和生成的GWAS数据 心脏研究所心力衰竭队列研究。此外，我们将从 Sami-Trop队列。综上所述，我们的努力将导致数量增加10倍以上 可以使用GWAS方法分析的chagas疾病的可用个体。 具体而言，我们建议通过以下特定目的解决此问题： 1。招募1,000名在Montes Claros，MG地区和 在来自Sami-Trop队列的2,000个样品中进行全基因组基因分型实验， 新的不确定形式组，来自巴西人的大约1,000个未生成的样本 Chagas心肌病遗传学的财团； 2.对参与该计划的不同GWAS研究进行荟萃分析； 3。确定和招募Cruzi的T. Cruzi感染了来自同一核心家庭的个人 Chagas心肌病的遗传力和未来的测序研究。