Genetic Admixture Study of Uterine Fibroids in African American Women

非裔美国女性子宫肌瘤的基因混合研究

基本信息

  • 批准号:
    7750614
  • 负责人:
  • 金额:
    $ 60.18万
  • 依托单位:
  • 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:
    2008-12-15 至 2012-11-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Uterine leiomyomata (UL), or fibroids, are a major source of gynecologic morbidity among reproductive-aged women. Relative to white women, black women are 2-3 times more likely to be diagnosed with UL, develop tumors at earlier ages, and have more severe disease at the time of diagnosis. Differences in environmental risk factors and screening behaviors do not explain this racial disparity. Using DNA from the Black Women's Health Study (BWHS), a nationwide follow-up study of 59,000 African American women begun in 1995, we propose to conduct genome-wide assays to identify genetic variants associated with clinically relevant UL. On follow-up questionnaires completed in 1997, 1999, 2001, 2003, and 2005, BWHS participants have reported data on the occurrence of incident UL and on a wide range of UL risk factors. A validation study of UL in the BWHS has demonstrated high accuracy of self-report (>96%). DNA samples have been obtained from over 26,000 BWHS participants, including 2,500 incident cases of UL. We propose to first use admixture mapping of 2,500 UL cases to find genes associated with UL that differ greatly in frequency across European and African populations. Admixture mapping has more power than linkage mapping in families to find genes of moderate effect. It is less expensive per sample than whole-genome association but has similar power to detect variants that differ across populations. Fine mapping in additional cases and matched controls, will be carried out if genome-wide suggestive or significant peaks are detected. If no such peaks are detected, we will carry out a whole-genome scan for UL genes in 768 UL cases and matched controls to detect variants that are not highly differentiated in frequency between African and European populations. Because gene-disease associations may be stronger among younger cases and those with greater symptomatology (markers of disease severity), we will prioritize the selection of younger surgically-confirmed cases. The controls will be restricted to those who reported a recent ultrasound (<5 years ago). Genes associated with UL in the BWHS will be tested in the NIEHS Fibroid Study to assess the robustness of our findings. The large number of incident UL cases in the BWHS will provide high statistical power. The study can be carried out at relatively low cost because the follow-up of BWHS participants and data collection, including the collection of DNA samples, are supported by other grants. The high incidence of UL in black women is a problem of major public health importance. The proposed study may identify genetic risk factors for UL that contribute to the large excess of the disease among black women. PUBLIC HEALTH RELEVANCE: Uterine leiomyomata (UL), or fibroids, are a major source of gynecologic morbidity among black women and account for more than $2.1 billion in U.S. health care costs each year. Using data from the Black Women's Health Study, a large prospective follow-up study of African American women, we propose to carry out genome-wide assays to identify genes that might contribute to the occurrence of clinically relevant UL in black women. The proposed study has great potential to help explain the excess incidence of UL among African American women.
描述(申请人提供):子宫肌瘤(UL),或肌瘤,是育龄妇女妇科发病率的主要来源。与白人女性相比,黑人女性被诊断为UL的可能性是白人女性的2-3倍,患肿瘤的年龄更早,而且在确诊时有更严重的疾病。环境风险因素和筛查行为的差异不能解释这种种族差异。利用黑人妇女健康研究(BWHS)的DNA,我们建议进行全基因组分析,以确定与临床相关的UL相关的基因变异。BWHS是一项始于1995年的全国性跟踪研究,对59,000名非裔美国女性进行了研究。在1997年、1999年、2001年、2003年和2005年完成的后续调查问卷中,BWHS参与者报告了UL事件的发生情况和各种UL风险因素的数据。BWHS对UL的验证研究表明,自我报告的准确率很高(&gt;96%)。已从26,000多名BWHS参与者那里获取了DNA样本,其中包括2,500例UL事件。我们建议首先使用2500例UL病例的混合图谱来寻找与UL相关的基因,这些基因在欧洲和非洲人群中的频率差异很大。在家系中,混合作图比连锁作图更能发现中等效应的基因。它比全基因组关联每个样本的成本更低,但在检测不同种群之间不同的变异方面具有类似的能力。如果检测到全基因组的提示峰或显著峰,将在其他病例和匹配的对照中进行精细作图。如果没有检测到这样的峰值,我们将对768例UL病例和匹配的对照组进行UL基因的全基因组扫描,以检测非洲和欧洲人群之间频率差异不高的变异。由于基因与疾病的相关性可能在较年轻的病例和症状较重的患者(疾病严重程度的标志)中更强,我们将优先选择较年轻的手术确诊病例。控制措施将仅限于那些报告最近(5年前)做过超声波检查的人。BWHS中与UL相关的基因将在NIEHS肌瘤研究中进行测试,以评估我们发现的稳健性。BWHS中大量的UL事件将提供很高的统计能力。这项研究可以以相对较低的费用进行,因为BWHS参与者的后续行动和数据收集,包括DNA样本的收集,都得到了其他赠款的支持。UL在黑人女性中的高发病率是一个重大的公共卫生问题。这项拟议的研究可能会确定UL的遗传风险因素,这些因素导致黑人女性中UL疾病的大量增加。公共卫生相关性:子宫肌瘤(UL),或称肌瘤,是黑人女性妇科疾病的主要来源,每年占美国医疗保健费用的21亿美元以上。利用黑人妇女健康研究的数据,我们建议进行全基因组分析,以确定可能与黑人妇女临床相关UL发生有关的基因。黑人妇女健康研究是一项针对非裔美国女性的大型前瞻性后续研究。这项拟议的研究具有巨大的潜力,可以帮助解释非裔美国女性UL的过度发病率。

项目成果

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LAUREN A WISE其他文献

LAUREN A WISE的其他文献

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{{ truncateString('LAUREN A WISE', 18)}}的其他基金

A preconception cohort study of environmental chemicals, fertility, and miscarriage
环境化学物质、生育力和流产的孕前队列研究
  • 批准号:
    10517495
  • 财政年份:
    2019
  • 资助金额:
    $ 60.18万
  • 项目类别:
Environmental risk factors for uterine fibroids: a prospective ultrasound study(Supplement)
子宫肌瘤的环境危险因素:一项前瞻性超声研究(补充)
  • 批准号:
    9907405
  • 财政年份:
    2017
  • 资助金额:
    $ 60.18万
  • 项目类别:
Environmental risk factors for uterine fibroids: a prospective ultrasound study
子宫肌瘤的环境危险因素:一项前瞻性超声研究
  • 批准号:
    9754823
  • 财政年份:
    2017
  • 资助金额:
    $ 60.18万
  • 项目类别:
Environmental risk factors for uterine fibroids: a prospective ultrasound study
子宫肌瘤的环境危险因素:一项前瞻性超声研究
  • 批准号:
    9361988
  • 财政年份:
    2017
  • 资助金额:
    $ 60.18万
  • 项目类别:
Environmental risk factors for uterine fibroids: a prospective ultrasound study
子宫肌瘤的环境危险因素:一项前瞻性超声研究
  • 批准号:
    10227933
  • 财政年份:
    2017
  • 资助金额:
    $ 60.18万
  • 项目类别:
An internet-based preconception cohort study in North America
北美基于互联网的孕前队列研究
  • 批准号:
    10680455
  • 财政年份:
    2016
  • 资助金额:
    $ 60.18万
  • 项目类别:
An internet-based preconception cohort study in North America
北美基于互联网的孕前队列研究
  • 批准号:
    10521733
  • 财政年份:
    2016
  • 资助金额:
    $ 60.18万
  • 项目类别:
Endocrine disrupting chemicals and risk of uterine fibroids: a prospective study
内分泌干​​扰化学物质与子宫肌瘤的风险:一项前瞻性研究
  • 批准号:
    8963998
  • 财政年份:
    2015
  • 资助金额:
    $ 60.18万
  • 项目类别:
Endocrine disrupting chemicals and risk of uterine fibroids: a prospective study
内分泌干​​扰化学物质与子宫肌瘤的风险:一项前瞻性研究
  • 批准号:
    9302417
  • 财政年份:
    2015
  • 资助金额:
    $ 60.18万
  • 项目类别:
Feasibility of an internet-based study of time-to-pregnancy in the United States
在美国基于互联网的怀孕时间研究的可行性
  • 批准号:
    8444099
  • 财政年份:
    2013
  • 资助金额:
    $ 60.18万
  • 项目类别:

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非裔美国人冠心病和相关代谢组标记物的混合图谱
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    2020
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非裔美国儿童急性淋巴细胞白血病的混合分析:ADMIRAL 研究
  • 批准号:
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  • 财政年份:
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非裔美国人缺血性中风的混合图谱
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