Methods for Epidemiology Studies

流行病学研究方法

• 批准号: 9549622
• 负责人: Paul Albert
• 金额: $ 281.99万
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 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/9549622
• 关键词: Address; Area; Biological Markers; Biometry; Blood; Breast; Breast Cancer Detection; Breast Cancer Education; Bronchi; Calibration; Cancer Detection; Categories; Cervical Cancer Screening; Colon; Colorectal Cancer; Complex; Computer software; Data; Data Analyses; Detection; Differential Equation; Dimensions; Disease; Division of Cancer Epidemiology and Genetics; Dose; Electronic Health Record; Environmental Risk Factor; Epidemiologic Methods; Equilibrium; Family; Genes; Genetic; Genetic Markers; Genomics; Genotype; Guidelines; Household; Individual; International; Left; Lung; Malignant neoplasm of lung; Measurement; Methods; Mission; Modeling; National Health and Nutrition Examination Survey; Outcome; Pathway Analysis; Pleura; Procedures; Rectum; Research; Risk; Risk Estimate; Sampling; Surveys; Testing; The Cancer Genome Atlas; Trachea; Vitamin D; Weight; base; design; disorder risk; electronic data; epidemiology study; genetic variant; improved; malignant breast neoplasm; member; method development; microbiome; novel; novel strategies; population based; protective effect; response; semiparametric; statistics; trait

Extensions of likelihood-based sufficient dimension reduction methods were proposed and studied for analyzing biomarkers that are left and/or right censored due to lower or upper limits of detection. These methods apply generally to any type of outcome, including continuous and categorical outcomes. Bias of estimates of exposure effects conditional on covariates was assessed when summary scores of confounders, instead of the confounders themselves, were used to analyze observational data. Two scores, the propensity score (PS) and the disease risk score (DRS) were studied in detail. New procedures were developed for seasonal adjustment and calibration of blood measurements of vitamin D to support the multicenter international Vitamin D Pooling Project for Breast and Colorectal Cancer. These methods were used to guide the analysis on the associations of blood levels of Vitamin D with the risk of breast and of colorectal cancer with findings that indicate protective effects for colorectal cancer. Parametric and semi-parametric mixture models have been proposed for analyzing left or interval-censored data from electronic health records. The new approach was used for risk estimates that underlie current U.S. risk-based cervical cancer screening guidelines. A multiple imputation approach based on Additive Regression, Bootstrapping and Predictive mean matching (ARBP) methods was introduced to accurately impute the missing values for steps collected in the 2003-2004 National Health and Nutrition Examination Survey NHANES. A novel class of functional data analysis models based hierarchical stochastic differential equations was developed to address some limitations by existing methods. An efficient Hardy Weinberg Equilibrium test was developed to analyze genetic data collected from population-based household surveys utilizing pairwise composite likelihood methods that incorporate the sample weighting effect and genetic correlation induced by the complex sample designs. A general procedure was developed for conducting gene and pathway analysis that uses only SNP-level summary statistics in combination with genotype correlations estimated from a reference panel of individual-level genetic data. A family of multi-locus testing procedures were developed for detecting the composite association between a set of genetic markers and two traits, based on a random effect model with two variance components, with each presenting the genetic effect on one trait. A likelihood-based test was developed for mutual exclusivity analysis in detection of cancer driver gene and applied to TCGA data, as well as a DCEG lung cancer study. A statistical framework and a computationally efficient software package were developed for identifying host genetic variants associated with microbiome beta diversity with or without interacting with an environmental factor.

提出了基于似然的足够降低方法的扩展，并研究了由于检测的下限或上限，用于分析左或右审查的生物标志物。这些方法通常适用于任何类型的结果，包括连续和分类结果。 当使用混杂因素而不是混杂因素本身的摘要得分来分析观察数据时，评估了对协变量有条件的暴露效应估计值的偏差。详细研究了两个分数，倾向评分（PS）和疾病风险评分（DRS）。开发了新的程序，用于调整维生素D的血液测量结果，以支持多中心国际维生素D综合乳腺癌和结直肠癌的项目。这些方法用于指导对维生素D与乳腺癌和大肠癌风险的关联的分析，并发现表明对大肠癌的保护作用。已经提出了参数和半参数混合模型，用于分析电子健康记录中的左或间隔经过的数据。新方法用于风险估计，这是美国当前基于风险的宫颈癌筛查指南的基础。 引入了基于添加剂回归，引导和预测平均匹配（ARBP）方法的多种插补方法，以准确地算出2003 - 2004年国家健康和营养检查调查NHANES中收集的步骤的缺失值。开发了基于层次的随机微分方程的新型功能数据分析模型，以通过现有方法来解决某些局限性。开发了一种有效的Harty Weinberg平衡检验，以分析利用成对复合可能性方法的基于人群的家庭调查收集的遗传数据，这些方法结合了样品加权效果和由复杂样品设计引起的遗传相关性。开发了进行基因和途径分析的一般程序，该程序仅使用SNP级汇总统计数据与从个人级遗传数据的参考面板估计的基因型相关性结合使用。开发了一个多层次测试程序，用于检测基于具有两个方差成分的随机效应模型，其中一组遗传标记和两个性状之间的综合关联，每种遗传效应对一个性状呈现。开发了基于可能性的测试，用于用于检测癌症驱动基因的相互排他性分析，并应用于TCGA数据以及DCEG肺癌研究。开发了一个统计框架和计算高效的软件包，用于识别与微生物组β多样性相关的宿主遗传变异，无论是否与环境因素相互作用。