Genetic epidemiology of complex diseases

复杂疾病的遗传流行病学

• 批准号: 7968948
• 负责人: Charles Rotimi
• 金额: $ 263.79万
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 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/7968948
• 关键词: 21 year old; 5q31; Admixture; Africa; African; African American; American; Area; Base Pairing; Bioinformatics; Biological; Biomedical Research; Blood Pressure; Boston; Candidate Disease Gene; China; Chromosome Mapping; Chromosomes; Clinical; Collaborations; Complex; Consent; Country; 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; Epidemiology; Ethiopia; Etiology; FGFR2 gene; Functional disorder; Genes; Genetic; Genetic Markers; Genetic Models; Genome; Genomics; Genotype; Ghana; Grant; Health; Height; Home environment; Human; Human Genome; Hypertension; Individual; Informed Consent; Inherited; Institutes; International; Journals; Kenya; Knowledge; Life Style; Light; Low income; Manuscripts; Maps; Methods; Mexican Americans; Mission; Modeling; Mutation Detection; National Institute of Diabetes and Digestive and Kidney Diseases; Nigeria; Obesity; Pattern; Pharmaceutical Preparations; Phenotype; Play; Policies; Population; Predisposition; Procedures; Process; Publishing; Research; Research Design; Research Personnel; Resources; Role; Sampling; San Francisco; Scientist; Services; Single Nucleotide Polymorphism; Soil; Students; Supervision; Susceptibility Gene; Texas; Training Programs; Translating; United States National Institutes of Health; Universities; Variant; Woman; Women' s Health; Work; case control; clay; cohort; density; design; epidemiology study; genetic epidemiology; genetic selection; genetic variant; genome wide association study; genome-wide; health disparity; human disease; malignant breast neoplasm; meetings; metropolitan; novel; population health; programs; response

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. We recently published the analyses of the Hypertension and blood pressure findings in the journal PLOS Genetics 2009 Jul;5(7)- "A genome-wide association study of hypertension and blood pressure in African Americans". 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 impute genotypes using the HapMap release #22 in 60 YRI (Yoruba) founders. This procedure increased the number of SNPs from 1,496 to over 22,000 resulting in a 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 shed light on the 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. We have ongoing large-scale genetic epidemiology studies that are designed to shed light on the complex interaction between genetic and environmental factors in the etiology of diabetes and associated complications in multiple African countries (Nigeria Ghana and Kenya), in Suizhou, China and among African Americans from Washington, DC and Mexican Americans from Houston, Texas. 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 a 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 association 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 study that will attempt 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 were sent to a commercial genotyping facility for genome-wide SNP genotyping. A total of 198 cases and 203 controls were genotyped using the Illumina HumanHap 610 Bead Chip which contains over 600,000 single nucleotide polymorphisms (SNPs). Resulting genome-wide association data is being analyzed by our PhD student (Fasil Tekola) under the supervision of Drs. Adeyemo and Rotimi. We recently published a manuscript detailing the informed consent process for this study entitled "Tailoring consent to context: designing an appropriate consent process for a biomedical study in a low income setting" in the journal PLoS Negl Trop Dis. 2009 Jul 21;3(7). The Black Women Health Study (BWHS): The CRGGH lab is collaborating with Boston University to develop a project to conduct a 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 by our collaborators to NIDDK to conduct a GWAS in 2000 cases of diabetes and 2000 controls. We recently submitted a manuscript titled "Novel region in the FGFR2 gene is associated with breast cancer in African American women" for review.

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。我们最近在《 PLOS Genetics 2009 Jul》杂志上发表了有关高血压和血压发现的分析； 5（7） - “全基因组全基因组的高血压和血压研究研究”。 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，我们使用插补程序使用HAPMAP版本22在60年（约鲁巴）创始人中估算基因型。该过程将SNP的数量从1,496个增加到22,000多个，导致遗传图（约11KB的1KB密度）。我们已经完成了该项目的分析，并确定了令人兴奋的肥胖和糖尿病的新型遗传变异，这些变异有望阐明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。 我们进行了持续的大规模遗传流行病学研究，旨在阐明多个非洲国家（尼日利亚加纳尼日利亚和肯尼亚）的糖尿病病因和相关并发症的遗传和环境因素之间的复杂相互作用，苏伊州，中国，中国以及来自华盛顿州德克萨斯州华盛顿州和墨西哥裔美国人的非裔美国人中的非裔美国人。 非裔美国人中高血压基因的混合图映射：CRGGH实验室正在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的密度SNP面板进行精细映射。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。 在非洲裔美国人和非洲人群中识别高血压敏感性基因的全面候选基因方法：CRGGH实验室已完成了一项大规模的候选基因研究，用于非洲裔美国人和多个非洲人人群中的高血压研究（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确定对HTN的易感性变异。 足球症的遗传学：与埃塞俄比亚和英国的科学家合作，CRGGH研究人员正在进行首个遗传流行病学研究，该研究将试图揭示基因与环境之间的相互作用，而在足病学的病因学（地方性非far虫）（地方性非律性质量）中。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，DNA样品被发送到用于全基因组SNP基因分型的商业基因分型设备。使用Illumina Humanhap 610珠芯片对总共进行了198例和203个对照，其中包含超过600,000个单核苷酸多态性（SNP）。在DRS的监督下，我们的博士生（Fasil Tekola）对全基因组关联数据进行了分析。 Adeyemo和Rotimi。我们最近发表了一份手稿，详细介绍了本研究的知情同意过程，题为“对上下文的裁缝同意：在低收入环境中为生物医学研究设计适当的同意过程”。 2009年7月21日； 3（7）。 《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例对照）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。我们的合作者已向NIDDK提交了R01赠款，以在2000年的糖尿病和2000个控制案例中进行GWAS。我们最近提交了一份题为“ FGFR2基因的新型区域与非洲裔美国妇女的乳腺癌相关的手稿”。