Epidemiology of Putative Causal Variants in the Multiethnic Cohort

多种族群体中假定的因果变异的流行病学

基本信息

批准号：
7913446
负责人：
LOIC LE MARCHAND
金额：
$ 101.85万
依托单位：
UNIVERSITY OF HAWAII AT MANOA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7913446
关键词：
9p24 African American Age at Menarche American Architecture Behavioral Biological Biological Markers Blood Body mass index Breast California Cardiovascular Diseases Case-Control Studies Characteristics Chronic Disease Clinical Clinical Data Clinical Trials Cohort Studies Collaborations Colorectal Cancer Commit Communities Complex DNA Data Data Analyses Databases Diabetes Mellitus Diet Disease Distant Elderly Endometrial Carcinoma Enhancers Ensure Environment Environmental Risk Factor Epidemiology Epigenetic Process Ethnic group European FGFR2 gene Fasting Funding Gene Expression Gene Frequency Genes Genetic Genetic Variation Genomics HMGA2 gene Hawaii Hawaiian population Health Height Heterogeneity Hip region structure Histone Acetylation Hormones Hyperlipidemia Insulin Intervention Investigation Japanese American Latino Life Style Link Lipids Lung Lymphocyte Malignant Neoplasms Malignant neoplasm of prostate Maps Measures Methylation Natural History Nested Case-Control Study Obesity Pancreas Pattern Phenotype Physical activity Plasma Population Population Heterogeneity Predisposition Prevalence Prospective Studies Prostate Race Reporting Research Research Design Research Personnel Resources Risk Risk Factors Signal Transduction Site Smoke Smoking Steroids Subgroup Transcript Tumor Cell Line Urine Variant Weight Woman Work analytical method base biobank cancer risk case control cohort data sharing disease characteristic disorder risk falls genetic association genetic variant genome wide association study insight lymphoblast malignant breast neoplasm men novel population based programs racial and ethnic response steroid hormone trait translational study

项目摘要

DESCRIPTION (provided by applicant): In response to RFA-HG-07-014, we propose to use the Multiethnic Cohort (MEC) study to characterize the "epidemiologic architecture" of putative causal variants identified in large-scale genomic association studies for a wide range of complex traits (chronic diseases, intermediate phenotypes and behavioral risk factors) across racial/ethnic populations. We have established a large biorepository of blood and urine (N=67,000) and cryopreserved lymphocytes (N=15,000) linked to extensive, prospectively collected risk factor (e.g., diet, smoking, physical activity), biomarker and clinical data, for five racial/ethnic groups in the MEC. This cohort study of over 215,000 men and women in Hawaii and California is unique in that it is population-based and includes large representations of older adults (45-75 yrs at baseline) for five US racial/ethnic groups (Japanese Americans, African Americans, European Americans, Latinos and Native Hawaiians) at varying risks of chronic diseases. We propose to study: 1) diseases for which we have DNA available for large numbers of cases and controls (breast, prostate, and colorectal cancer, diabetes, and obesity); 2) important cancers that are less common (e.g., lung, pancreas, endometrial cancers, NHL) but for which we propose to pool our data with other funded groups; 3) common traits that are risk factors for these diseases (e.g., body mass index/weight, waist-to-hip ratio, height) and 4) relevant disease-associated biomarkers (e.g., fasting insulin and lipids, steroid hormones). Our specific aims are: 1) To determine the population-based epidemiologic profile (allele frequency, main effect, heterogeneity by disease characteristics) of putative causal variants in the five racial/ethnic groups in the MEC; 2) for variants displaying effect heterogeneity across ethnic/racial groups, we will utilize differences in LD to identify a more complete spectrum of associated variants at these loci; 3) investigate gene x gene and gene x environment interactions to identify modifiers; 4) examine the associations of putative causal variants with already measured intermediate phenotypes (e.g., plasma insulin, lipids, steroid hormones); and 4) for variants that do not fall within known genes, start to investigate their relationships with gene expression and epigenetic patterns in small genomic studies. We will coordinate the selection of these variants and endpoints, analytical methods, data analyses, and rapid reporting of results with other cohorts/clinical trials funded through this RFA.

描述（由申请人提供）：为了响应RFA-HG-07-014，我们建议使用多民族队列（MEC）研究来表征在大规模基因组研究中鉴定出的假定因果变体的“流行病学结构”，以实现复杂疾病的广泛范围（慢性疾病/跨越范围）的范围（慢性疾病/行为范围）。我们已经建立了大量的血液和尿液生物措施（n = 67,000）和冷冻保存的淋巴细胞（n = 15,000）（n = 15,000），与MEC中的五个种族/族裔群体有关，与广泛的，前瞻性地收集的危险因素（例如饮食，吸烟，体育活动），生物标志物和临床数据有关。这项对夏威夷和加利福尼亚州超过215,000名男女的队列研究是独一无二的，因为它是基于人群的，并且包括对五个美国种族/族裔群体（日裔美国人，非裔美国人，欧洲人，拉丁美洲人，拉丁裔夏威夷人和夏威夷人）的老年人（基线为45-75岁）的大量代表。我们建议研究：1）为大量病例和对照（乳腺癌，前列腺癌和大肠癌，糖尿病和肥胖症）提供DNA的疾病； 2）重要的癌症的重要癌症（例如肺，胰腺，子宫内膜癌，NHL），但我们建议与其他资助的群体一起汇集数据； 3）是这些疾病的危险因素（例如体重指数/体重，腰围比，身高）和4）相关疾病相关的生物标志物（例如禁食胰岛素和脂质，类固醇激素）的常见特征。我们的具体目的是：1）确定MEC中五个种族/族裔群体中假定的因果变异的基于人群的流行病学特征（等位基因频率，主要作用，疾病特征异质性）； 2）对于在种族/种族群体之间显示效应异质性的变体，我们将利用LD的差异来确定这些基因座的相关变体的更完整的频谱； 3）研究基因X基因和基因X环境相互作用以识别修饰符； 4）检查推定因果变异与已经测量的中间表型（例如血浆胰岛素，脂质，类固醇激素）的关联； 4）对于不属于已知基因的变体，在小型基因组研究中开始研究它们与基因表达和表观遗传模式的关系。我们将协调这些变体和终点，分析方法，数据分析以及结果的快速报道以及通过此RFA资助的其他同龄人/临床试验的快速报告。