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：
7849597
负责人：
LOIC LE MARCHAND
金额：
$ 168.86万
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：
2008
资助国家：
美国
起止时间：
2008-07-17 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7849597
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 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 Waist-Hip Ratio 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）：针对 RFA-HG-07-014，我们建议使用多种族队列 (MEC) 研究来表征大规模基因组关联研究中确定的假定因果变异的“流行病学结构”跨种族/族裔人群的广泛复杂特征（慢性疾病、中间表型和行为风险因素）。我们建立了一个大型生物样本库，其中包含五个种族的血液和尿液 (N=67,000) 以及冷冻保存的淋巴细胞 (N=15,000)，与广泛的、前瞻性收集的危险因素（例如饮食、吸烟、体力活动）、生物标志物和临床数据相关联。 /MEC 中的族裔群体。这项对夏威夷和加利福尼亚州超过 215,000 名男性和女性进行的队列研究的独特之处在于，它以人口为基础，并且包括美国五个种族/族裔群体（日裔美国人、非裔美国人）的大量老年人（基线为 45-75 岁）。、欧洲裔美国人、拉丁裔和夏威夷原住民）面临不同程度的慢性病风险。我们建议研究： 1) 我们拥有大量病例和对照 DNA 的疾病（乳腺癌、前列腺癌、结直肠癌、糖尿病和肥胖症）； 2) 不太常见的重要癌症（例如肺癌、胰腺癌、子宫内膜癌、非霍奇金淋巴瘤），但我们建议将我们的数据与其他资助团体的数据进行汇总； 3) 作为这些疾病危险因素的共同特征（例如，体重指数/体重、腰臀比、身高）和 4) 与疾病相关的生物标志物（例如，空腹胰岛素和血脂、类固醇激素）。我们的具体目标是： 1) 确定 MEC 中五个种族/民族的假定因果变异的基于人群的流行病学特征（等位基因频率、主效应、疾病特征的异质性）； 2) 对于在不同民族/种族群体中表现出效应异质性的变异，我们将利用 LD 的差异来识别这些位点上更完整的相关变异谱； 3）研究基因x基因和基因x环境相互作用以确定修饰因子； 4) 检查假定的因果变异与已测量的中间表型（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异，开始在小型基因组研究中研究它们与基因表达和表观遗传模式的关系。我们将与通过本 RFA 资助的其他队列/临床试验协调这些变异和终点的选择、分析方法、数据分析以及结果的快速报告。