GENETIC EPIDEMIOLOGY OF ENDOMETRIOSIS

子宫内膜异位症的遗传流行病学

基本信息

批准号：
8173135
负责人：
CATHERINE ANNE MCCARTY
金额：
$ 3.1万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2011-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8173135
关键词：
Age Animal Model Animals Anus Clinic Collaborations Computer Retrieval of Information on Scientific Projects Database Computerized Medical Record Coupled DNA Data Diagnosis Discipline of obstetrics Disease Electronics Endocrine Enrollment Environmental Risk Factor Evaluation Family history of Female Fertility Formalin Funding Gene Frequency Genetic Genetic Markers Genetic Predisposition to Disease Genomics Grant Gynecology Head Health Services Research Histology Human Image Institution Location Macaca mulatta Malignant Neoplasms Medical Medicine Mineral Oil Monkeys Morphology Nuclear Family Online Systems Operative Surgical Procedures Outcome Paraffin Embedding Patient Self-Report Patients Physical activity Physiology Prevalence Primates Publications Quality of life Questionnaires Recording of previous events Recruitment Activity Recurrence Research Research Personnel Research Project Grants Resources Risk Risk Factors Sampling Scientist Services Siblings Smoking History Source Specimen Surveys Time Treatment Factor United States United States National Institutes of Health Universities Update Woman biobank cohort disorder risk endometriosis genetic association genetic epidemiology genetic pedigree nonhuman primate population based professor

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To investigate the genetic epidemiology of endometriosis. While the cause remains unknown, there is a clear familial aggregation of endometriosis in both humans and non-human primates. In the proposed project, a multigenerational pedigree of rhesus monkeys demonstrating spontaneous disease with identical morphology and histology to that seen in women will serve as the animal model for genetic studies. This data will be coupled with the specimens and electronic medical records of patients previously diagnosed with endometriosis to verify genetic markers identified in the monkey pedigree. The pedigree was updated and refined by Kirsten Geraedts. The five specific aims of the project are to: 1) Confirm the diagnosis of endometriosis in 937 women with electronic diagnoses of endometriosis enrolled in the Personalized Medicine Research Project (PMRP). This is the largest population-based DNA biobank in the United States; it allows population-based estimates of allele frequencies and genetic associations. 2) Recruit additional women with surgically confirmed endometriosis into the PMRP cohort to reach a target of 1000 cases. 3) Administer validated endometriosis quality of life questionnaires to the women with confirmed endometriosis and document self-reported family history of endometriosis. 4) Quantify known risk factors (age, smoking history, physical activity, family history of endometriosis, endocrine factors), treatments (medical and surgical), and known outcomes (cancers, reduced fertility) in women with endometriosis. 5) Describe the genetic epidemiology of endometriosis in this cohort using the information collected in Aim 1. The Primate Center has a long history of investigating the prevalence and familial aggregation of endometriosis in rhesus macaques. Between 1978 and 2002, WNPRC researchers identified 144 rhesus macaques with endometriosis. They established a large multigenerational pedigree and nine nuclear families comprising 1,602 females. They found that the prevalence of endometriosis increased with age. In addition, they saw a higher recurrence risk for full siblings when compared to maternal half siblings and paternal half sibs. Those studies were led by Stephen Kennedy, head of the Nuffield Department of Obstetrics and Gynecology at Oxford University, and Joe Kemnitz, WNRPC director and professor of physiology. They focused on the mode of inheritance, location of potential genetic susceptibility loci, and the influence of environmental factors on disease risk. Ricki Colman, now a WNPRC associate scientist, conducted the non-invasive imaging studies at the time. The Marshfield Clinic collaboration continues this evaluation of pedigree and genetic information. The project is also expanding to include a web-based survey of the prevalence of endometriosis in the colonies of the other National Primate Research Centers. This project uses WNPRC Animal Services and Research Services. PUBLICATION: Lin J, Kennedy SH, Svarovsky T, Rogers J, Kemnitz JW, Xu A, Zondervan KT. High-quality genomic DNA extraction from formalin-fixed and paraffin-embedded samples deparaffinized using mineral oil. Anal Biochem. 2009 Dec 15;395(2):265-7. Epub 2009 Aug 19.

该子项目是利用该技术的众多研究子项目之一资源由 NIH/NCRR 资助的中心拨款提供。子项目及研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金，因此可以在其他 CRISP 条目中表示。列出的机构是对于中心来说，它不一定是研究者的机构。目的：探讨子宫内膜异位症的遗传流行病学。虽然病因尚不清楚，但人类和非人类灵长类动物的子宫内膜异位症均存在明显的家族聚集性。在拟议的项目中，恒河猴的多代谱系表现出与女性相同的形态和组织学的自发疾病，将作为遗传研究的动物模型。这些数据将与先前诊断为子宫内膜异位症的患者的标本和电子病历相结合，以验证猴子谱系中发现的遗传标记。克尔斯滕·杰拉兹 (Kirsten Geraedts) 更新并完善了血统书。该项目的五个具体目标是： 1) 对参加个性化医疗研究项目 (PMRP) 的 937 名接受子宫内膜异位症电子诊断的女性确认子宫内膜异位症的诊断。这是美国最大的基于人群的 DNA 生物库；它允许基于人群的等位基因频率和遗传关联的估计。 2) 招募更多经手术确诊患有子宫内膜异位症的女性加入 PMRP 队列，以达到 1000 例的目标。 3) 对确诊子宫内膜异位症的女性进行经过验证的子宫内膜异位症生活质量调查问卷，并记录自我报告的子宫内膜异位症家族史。 4) 量化子宫内膜异位症女性的已知风险因素（年龄、吸烟史、体力活动、子宫内膜异位症家族史、内分泌因素）、治疗（药物和手术）和已知结果（癌症、生育能力下降）。 5) 使用目标 1 中收集的信息描述该队列中子宫内膜异位症的遗传流行病学。灵长类动物中心在研究恒河猴子宫内膜异位症的患病率和家族聚集性方面有着悠久的历史。 1978 年至 2002 年间，WNPRC 研究人员发现 144 只恒河猴患有子宫内膜异位症。他们建立了一个庞大的多代血统和九个核心家庭，其中包括 1,602 名女性。他们发现子宫内膜异位症的患病率随着年龄的增长而增加。此外，他们发现，与同母异父的兄弟姐妹和同父异母的兄弟姐妹相比，同父异母的兄弟姐妹的复发风险更高。这些研究由牛津大学纳菲尔德妇产科主任 Stephen Kennedy 和 WNRPC 主任兼生理学教授 Joe Kemnitz 领导。他们重点关注遗传模式、潜在遗传易感位点的位置以及环境因素对疾病风险的影响。 Ricki Colman，现任 WNPRC 副科学家，当时进行了非侵入性成像研究。马什菲尔德诊所的合作继续对谱系和遗传信息进行评估。该项目还正在扩展，包括对其他国家灵长类动物研究中心的群体子宫内膜异位症患病率进行网络调查。该项目使用 WNPRC 动物服务和研究服务。发布： Lin J，Kennedy SH，Svarovsky T，Rogers J，Kemnitz JW，Xu A，Zondervan KT。从使用矿物油脱蜡的福尔马林固定和石蜡包埋的样品中提取高质量的基因组 DNA。肛门生物化学。 2009 年 12 月 15 日；395(2):265-7。电子版 2009 年 8 月 19 日。