Genetic epidemiology of complex diseases

复杂疾病的遗传流行病学

基本信息

批准号：
7734929
负责人：
Charles Rotimi
金额：
$ 170万
依托单位：
NATIONAL HUMAN GENOME RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7734929
关键词：
5q31 Admixture Africa African African American Age American Area Base Pairing Bioinformatics Biological Biomedical Research Boston Candidate Disease Gene Chromosome Mapping Chromosomes Clinical Collaborations Complex Custom DNA DNA Resequencing Data Databases Diabetes Mellitus Disease Disease susceptibility District of Columbia Doctor of Philosophy Elephantiasis Employee Strikes Enrollment Environment Environmental Risk Factor Ethiopia Etiology Functional disorder Genes Genetic Genetic Markers Genetic Models Genome Genomics Genotype Grant Health Height Home environment Human Human Genome Hypertension Individual Inherited Institutes International Knowledge Life Style Light Manuscripts Maps Methods Mission Modeling Mutation Detection National Institute of Diabetes and Digestive and Kidney Diseases Numbers Obesity Pattern Pharmaceutical Preparations Phenotype Play Policies Population Predisposition Procedures Process Research Research Personnel Resources Role Sampling San Francisco Scientist Services Soil Staging Students Susceptibility Gene Thinking Training Programs Translating United States National Institutes of Health Universities Variant Woman Women&apos s Health Work case control clay cohort density genetic epidemiology genetic selection genetic variant genome wide association study health disparity human disease metropolitan novel programs response

项目摘要

Genome Wide Association Studies (GWAS): In collaboration with investigators at the Coriell Institute for Biomedical Research, the CRGGH lab has successfully completed a genome-wide scan of over 2000 African Americans using the Affymetrix Genome-Wide Human SNP Array 6.0 with 1.8 million genetic markers ( equal number of SNPs and CNVs). Investigators at the center are currently analyzing generated data on multiple phenotypes including obesity, hypertension, diabetes and height. Resulting manuscripts are at different stages of completion. Fine-mapping of Diabetes Genes: The CRGGH lab is conducting fine mapping of a linkage region on chromosome 5q22-5q31 (109055750 128436401 base pairs). Genotyping for this project was conducted by the Center for Inherited Disease Research (CIDR) using the Illumina Custom infinium II BeadChip. A total of 1,536 SNPs were attempted and 1,496 SNPs were released. In addition, we used the Imputation procedure to imputed genotypes using the HapMap release #22 in 60 YRI (Yoruba) founder. This procedure increased the number of SNPs from 1,496 to over 22,000 resulting in much denser genetic map ( 1kb density from about 11kb). We have completed analyses of this project and we have identified exciting novel genetic variants for obesity and diabetes that promises to share light on pathophysiology of these human diseases. The manuscripts describing these findings are complete and we are awaiting the results of the replication projects in other populations. The initial results were presented recently in San Francisco during the 2008 American Diabetes Association annual meeting. Admixture Mapping for Hypertension Genes in African Americans The CRGGH lab is using the admixture mapping approach to identify regions of the genome that may harbor hypertension susceptibility genes in African Americans. We have genotyped a panel of over 3,000 ancestry informative markers in a well-characterized cohort of African Americans enrolled from the Washington, D.C. metropolitan area. This data is being analyzed by investigators at the CRGGH lab. Identified susceptibility loci will be subjected to fine mapping using very high density SNP panel selected from the HapMap database. In combination with bioinformatics methods, the CRGGH lab will use the data from the fine-mapping studies to identify genes to be resequenced for mutation detection and replication studies in multiple populations. Comprehensive Candidate Gene Approach to Identify Hypertension Susceptibility Genes in African Americans and African Populations - The CRGGH lab has completed a large-scale candidate genes study for hypertension (HTN) in African Americans and multiple African populations. A total number of 1598 subjects (comprising 1002 African Americans and 562 West Africans) have been genotyped using Illuminas custom SNP GoldenGate genotyping platform. Given the poor consistency of candidate gene studies for HTN, we gave careful thought to the selection of genetic variants represented in the final custom panel of 768 SNPs. Investigators in the center are using the case-control associations strategy, under various genetic models, to identify susceptibility variants to HTN. Genetics of Podoconiosis: In collaboration with scientists from Ethiopia and the UK, CRGGH investigators are conducting the first genetic epidemiology to unravel the complex interaction between genes and environment in the etiology of podoconiosis (endemic non-filarial elephantiasis). Podoconiosis is a geochemical disease occurring in individuals exposed to red clay soil derived from alkalic volcanic rock. One of the striking features of podoconiosis is that only a small proportion of individuals who are exposed to red clay develop disease. The field work for this project is complete and DNA samples are being prepared for shipment to a commercial genotyping facility. Resulting data will be used as PhD thesis for the Ethiopian Student in the CRGGH lab. The Black Women Health Study (BWHS) The CRGGH lab is collaborating with Boston University to develop a project to conduct genome-wide association study in 4,000 African American women (2,000 cases of diabetes and 2,000 controls) in the BWHS. The BWHS is a national longitudinal cohort of women assembled in 1995 to study causes of illness in black women. It includes 59,000 women aged 21-69 at baseline. Dr. Rotimis lab was responsible for receiving, isolating and tracking DNA samples on these women. Over 25,000 DNA samples have been processed to date. An R01 grant has been submitted to NIDDK to conduct GWAS in 2000 cases of diabetes and 2000 controls.

基因组广泛的协会研究（GWAS）：与科里尔生物医学研究所的研究人员合作，CRGGH实验室成功地完成了使用1800万个遗传标记的Affymetrix基因组6.0的2000多名非裔美国人的全基因组扫描（SNP和CNV的数量相等）。该中心的研究人员目前正在分析有关多种表型的生成数据，包括肥胖，高血压，糖尿病和身高。由此产生的手稿处于完成的不同阶段。糖尿病基因的精细图：CRGGH实验室正在对染色体5Q222-5Q31上的连锁区域进行精细映射（109055750 128436401碱基对）。该项目的基因分型是由遗传疾病研究中心（CIDR）使用Illumina Custom Infinium II Beadchip进行的。总共尝试了1,536个SNP，并释放了1,496个SNP。此外，我们使用归档程序使用60年（约鲁巴）创始人的HAPMAP版本22进行估算的基因型。该过程将SNP的数量从1,496个增加到22,000多个，导致了许多较密集的遗传图（约11KB的1KB密度）。我们已经完成了对该项目的分析，并确定了令人兴奋的肥胖和糖尿病的新型遗传变异，这些变异有望分享这些人类疾病的病理生理学。描述这些发现的手稿已经完成，我们正在等待其他人群中复制项目的结果。最初的结果最近在2008年美国糖尿病协会年会期间在旧金山呈现。在非洲裔美国人中，CRGGH实验室的混合映射使用混合映射方法来识别可能具有非裔美国人中高血压易感基因的基因组区域。我们已经在华盛顿特区大都市地区入学的一个良好特征的非洲裔美国人中，组成了3,000多名祖先信息标记的小组。该数据正在由CRGGH实验室的研究人员分析。确定的敏感性基因座将使用从HAPMAP数据库中选择的非常高密度的SNP面板进行细微映射。结合生物信息学方法，CRGGH实验室将使用精细映射研究的数据来识别多个人群中的突变检测和复制研究的基因。 CRGGH实验室已经完成了一项大规模的候选基因研究（HTN），以识别非洲裔美国人和非洲人口中的高血压敏感性基因的全面候选基因方法（HTN）。使用Illuminas Custom SNP Goldengate基因分型平台对1598名受试者（包括1002名非裔美国人和562个西非人组成）的受试者总数。鉴于HTN候选基因研究的一致性差，我们对768 SNP的最终自定义面板中代表的遗传变异的选择进行了仔细的思考。该中心的研究人员正在使用各种遗传模型下的病例对照关联策略来识别对HTN的易感性变体。哥哥结构症的遗传学：与埃塞俄比亚和英国的科学家合作，CRGGH研究人员正在进行第一个遗传流行病学，以揭示基因与环境之间的相互作用的相互作用，而在podoconiosis的病因学中（特有非far虫属性属性）。足球病是一种地球化学疾病，发生在暴露于碱性火山岩的红色粘土土壤中。哥哥结构病的惊人特征之一是，暴露于红粘土的人中只有一小部分患者会发展出疾病。该项目的现场工作是完整的，并且正在为DNA样品准备运送到商业基因分型设施。结果数据将用作CRGGH实验室中埃塞俄比亚学生的博士学位论文。黑人妇女健康研究（BWHS）CRGGH实验室正在与波士顿大学合作，开发了一个项目，以在BWHS中对4,000名非裔美国妇女（2,000例糖尿病和2,000例）进行全基因组协会研究。 BWHS是1995年组建的全国妇女纵向队列，研究黑人妇女的疾病原因。它包括59,000名基线时21-69岁的妇女。 Rotimis Lab博士负责接收，隔离和跟踪这些女性的DNA样品。迄今为止，已经处理了超过25,000个DNA样品。在2000年的糖尿病和2000例对照病例中，已向NIDDK提交了R01赠款，以进行GWAS。