Genome-Wide Study of Cataract and Low HDL in the Personalized Medicine Research P

个性化医学研究中白内障和低 HDL 的全基因组研究

基本信息

批准号：
7427373
负责人：
CATHERINE ANNE MCCARTY
金额：
$ 79.16万
依托单位：
MARSHFIELD CLINIC RESEARCH FOUNDATION
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-27 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7427373
关键词：
Adult Algorithms Aliquot Architecture Back Caring Cataract Cataract Extraction Clinic Cohort Studies Communities Complex Computerized Medical Record Condition Confidentiality Consultations Data Data Compromising Data Security Depth Development Disease Electronics Enrollment Environment Environmental Risk Factor Etiology Funding Genes Genetic Genetic Markers Genome Genomics Goals High Density Lipoprotein Cholesterol High Density Lipoproteins Human Genome Human Genome Project Length Lipids Medicine Nested Case-Control Study Newsletter Outcome Outcome Study Pharmacogenetics Phenotype Plasma Population Positioning Attribute Prevalence Prevention Public Health Research Research Infrastructure Research Institute Research Personnel Research Project Grants Resources Risk Factors Site Standards of Weights and Measures Time Vision aged base care systems case control cigarette smoking clinical phenotype cohort design gene environment interaction gene interaction genetic association genetic epidemiology genetic risk factor genome wide association study novel

项目摘要

DESCRIPTION (provided by applicant): The primary goals of this project are to develop and validate electronic phenotyping algorithms, to accurately identify cases and controls, and to conduct a genome wide association study that advances understanding of two specific yet interrelated disease states, while simultaneously engaging the community in these research efforts. A secondary goal is to build upon the existing infrastructure necessary to further subsequent genome wide studies, positioning the PMRP biobank as a national resource. Lipid abnormalities and cataracts are both diseases of public health significance, they share common risk factors (and prevention or management with statins), and they are both complex diseases which likely have many genes contributing to disease development. Whole genome association studies with these two outcomes and environmental risk factors could yield novel data about the etiology of the two separate outcomes as well as their interaction. The specific aims of the study are as follows: 1a) to develop and validate two primary outcomes, low HDL and cataract, in the Marshfield Clinic PMRP, and to quantify the impact of two environmental factors (cigarette smoking and statin use) known to influence each of the primary study outcomes, 1b) to evaluate the validity of electronic algorithms developed in the context of different electronic medical records in the Marshfield Clinic EMR, 1c) in conjunction with the other funded sites, to develop standards for electronic phenotyping, 2) to conduct community consultation activities, define issues essential to the appropriate conduct of whole genome association studies, and maximize data sharing without compromising data security or confidentiality, 3a) elucidate combinations of genetic markers that predispose subjects to the development of cataract, 3b) further our understanding of the genetic architecture underlying low circulating levels of HDL cholesterol, and 3c) quantify the degree to which low HDL levels contribute to the onset and progression of cataracts in this population-based cohort, and to parse the genetic risk factors identified through whole genome scanning as being contributory to either low HDL cataract, or both, and explore gene/environment interaction with cigarette smoking and statin use. These aims will be studied in a nested case control study of 4220 cases (3037 low HDL, 1609 cataract surgery, 426 with both conditions) and 1481 controls aged 55 and older who have neither condition and have been screened for both conditions in the past five years. Quarterly meetings of the PMRP Community Advisory Group and quarterly newsletters will be used to engage and inform the public about this whole genome association study and the sharing of data with the wider research community. Multi-factor dimensionality reduction analyses will be used to prioritize SNPs for replication in other cohorts. The strength of the research team and the depth and breadth of the electronic medical record at the Marshfield Clinic make this the ideal setting for this RFA.

描述（由申请人提供）：该项目的主要目标是开发和验证电子表型分析算法，准确识别病例和对照，并进行全基因组关联研究，以增进对两种特定但相互关联的疾病状态的理解，同时让社区参与这些研究工作。第二个目标是建立进一步后续全基因组研究所需的现有基础设施，将 PMRP 生物库定位为国家资源。脂质异常和白内障都是具有公共卫生意义的疾病，它们具有共同的危险因素（以及用他汀类药物预防或治疗），并且它们都是复杂的疾病，可能有许多基因导致疾病的发展。对这两种结果和环境风险因素进行的全基因组关联研究可以产生关于这两种不同结果的病因学及其相互作用的新数据。该研究的具体目标如下： 1a) 在 Marshfield Clinic PMRP 中开发和验证两个主要结局，即低 HDL 和白内障，并量化已知影响的两个环境因素（吸烟和他汀类药物的使用）的影响每项主要研究成果，1b) 评估在 Marshfield Clinic EMR 的不同电子病历背景下开发的电子算法的有效性，1c) 与其他资助站点结合，制定电子病历标准表型分析，2) 开展社区咨询活动，确定适当进行全基因组关联研究所必需的问题，并在不损害数据安全性或保密性的情况下最大限度地共享数据，3a) 阐明使受试者易患白内障的遗传标记组合， 3b) 进一步了解低 HDL 胆固醇循环水平背后的遗传结构，3c) 量化低 HDL 水平对白内障发病和进展的影响程度基于人群的队列，并解析通过全基因组扫描确定的导致低 HDL 白内障或两者的遗传风险因素，并探索基因/环境与吸烟和他汀类药物使用的相互作用。这些目标将在一项巢式病例对照研究中进行研究，该研究涉及 4220 例病例（3037 例低 HDL，1609 例白内障手术，426 例患有这两种疾病）和 1481 名年龄在 55 岁及以上的对照者，这些对照者既没有患有这两种疾病，也没有在过去五年中接受过这两种疾病的筛查。年。 PMRP 社区咨询小组的季度会议和季度通讯将用于吸引公众并向公众通报这项全基因组关联研究以及与更广泛的研究社区共享数据。多因素降维分析将用于确定 SNP 在其他队列中复制的优先顺序。 Marshfield Clinic 的研究团队实力以及电子病历的深度和广度使其成为本次 RFA 的理想场所。