Genetic Epidemiology of Age-Related Macular Degeneration

年龄相关性黄斑变性的遗传流行病学

基本信息

  • 批准号:
    7319253
  • 负责人:
  • 金额:
    $ 55.34万
  • 依托单位:
  • 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:
    2007-09-30 至 2012-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD), the leading cause of incurable blindness among older adults in the US, is caused by interactions between underlying genetic susceptibility and lifestyle risk factors. However, our knowledge of the network of contributors to the pathogenesis of AMD remains incomplete, and treatment is inadequate. The proposed studies build upon a strong and growing foundation of research and invaluable existing resources to comprehensively study the genetic epidemiology of AMD. Through its use of archived DNA specimens from several large prospective cohort studies, this proposal represents a cost-effective, efficient, and informative approach to investigate the following specific aims: 1) determine the incidence rate ratio and attributable fraction for AMD in relation to common variants within a group of strong candidate genes including complement factor H, HTRA1/LOC387715, and others (candidates identified based on position, function, expression, etc.) using both single locus and haplotype analyses for AMD overall as well as for both dry and neovascular subtypes, 2) effectively utilize data derived from RNA microarray analysis of sibpairs extremely discordant for AMD to inform selection of candidate genes, 3) estimate the magnitude and significance of any gene-gene, or gene-environment interactions among these candidates and risk factors such as cigarette smoking, obesity, diet, and serum inflammatory markers. These aims will be accomplished through genotyping of >1300 confirmed incident AMD cases and >3000 controls in our high-tech core genotyping facility, along with direct sequencing when indicated for SNP discovery as well as to search for functional variants or disease-causing mutations if association analyses are significant. Unique strengths of this approach include the prospective design, large sample size, high-quality, high-throughput genotyping, integration with a study of extremely discordant sib-pairs, and state-of-the-art statistical analyses to provide precise estimates for effects of genes, gene-gene and gene-environment interactions. The proposed studies minimize bias through prospective assessment of exposures and AMD status, direct estimation of incidence rate ratios, novel candidate gene selection, and high statistical power. The long-term objective and clinical relevance of this research is to shed light on underlying biological mechanisms relevant to AMD, to suggest avenues for novel preventive or therapeutic approaches, and identify clinically useful risk assessments.
描述(由申请人提供):视网膜相关性黄斑变性(AMD)是美国老年人不可治愈失明的主要原因,由潜在遗传易感性和生活方式风险因素之间的相互作用引起。然而,我们对AMD发病机制的贡献者网络的了解仍然不完整,治疗也不充分。拟议的研究建立在一个强大的和不断增长的研究基础和宝贵的现有资源,全面研究AMD的遗传流行病学。通过使用来自几项大型前瞻性队列研究的存档DNA标本,该提案代表了一种具有成本效益,高效和信息丰富的方法,以调查以下具体目标:1)确定与一组强候选基因内的常见变体相关的AMD的发病率比和可归因分数,所述强候选基因包括补体因子H、HTRA 1/LOC 387715,以及其他(基于位置、功能、表情等确定的候选人)对AMD总体以及干性和新生血管亚型使用单基因座和单倍型分析,2)有效地利用来自AMD极不一致的同胞对的RNA微阵列分析的数据来告知候选基因的选择,3)估计这些候选基因和风险因素如吸烟、肥胖、饮食,和血清炎症标志物。这些目标将通过在我们的高科技核心基因分型设施中对>1300例确诊的AMD事件病例和>3000例对照进行基因分型来实现,沿着直接测序(当指示SNP发现时)以及搜索功能变体或致病突变(如果关联分析显著)。这种方法的独特优势包括前瞻性设计,大样本量,高质量,高通量基因分型,与极不一致的同胞对的研究相结合,以及最先进的统计分析,以提供对基因,基因-基因和基因-环境相互作用的影响的精确估计。拟议的研究通过对暴露和AMD状态的前瞻性评估、直接估计发病率比、新的候选基因选择和高统计功效来最大限度地减少偏倚。这项研究的长期目标和临床意义是阐明与AMD相关的潜在生物学机制,提出新的预防或治疗方法的途径,并确定临床有用的风险评估。

项目成果

期刊论文数量(0)
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DEBRA A SCHAUMBERG其他文献

DEBRA A SCHAUMBERG的其他文献

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{{ truncateString('DEBRA A SCHAUMBERG', 18)}}的其他基金

Omega-3 Fatty Acids for Prevention of Dry Eye Disease: VITAL-DED
用于预防干眼病的 Omega-3 脂肪酸:VITAL-DED
  • 批准号:
    8343444
  • 财政年份:
    2012
  • 资助金额:
    $ 55.34万
  • 项目类别:
Omega-3 Fatty Acids for Prevention of Dry Eye Disease: VITAL-DED
用于预防干眼病的 Omega-3 脂肪酸:VITAL-DED
  • 批准号:
    8534136
  • 财政年份:
    2012
  • 资助金额:
    $ 55.34万
  • 项目类别:
Omega-3 Fatty Acids for Prevention of Dry Eye Disease: VITAL-DED
用于预防干眼病的 Omega-3 脂肪酸:VITAL-DED
  • 批准号:
    8708876
  • 财政年份:
    2012
  • 资助金额:
    $ 55.34万
  • 项目类别:
Omega-3 Fatty Acids for Prevention of Dry Eye Disease: VITAL-DED
用于预防干眼病的 Omega-3 脂肪酸:VITAL-DED
  • 批准号:
    8916119
  • 财政年份:
    2012
  • 资助金额:
    $ 55.34万
  • 项目类别:
Genetic Epidemiology of Age-Related Macular Degeneration
年龄相关性黄斑变性的遗传流行病学
  • 批准号:
    8146031
  • 财政年份:
    2007
  • 资助金额:
    $ 55.34万
  • 项目类别:
Genetic Epidemiology of Age-Related Macular Degeneration
年龄相关性黄斑变性的遗传流行病学
  • 批准号:
    7683199
  • 财政年份:
    2007
  • 资助金额:
    $ 55.34万
  • 项目类别:
Genetic Epidemiology of Age-Related Macular Degeneration
年龄相关性黄斑变性的遗传流行病学
  • 批准号:
    7920034
  • 财政年份:
    2007
  • 资助金额:
    $ 55.34万
  • 项目类别:
Genetic Epidemiology of Age-Related Macular Degeneration
年龄相关性黄斑变性的遗传流行病学
  • 批准号:
    7501904
  • 财政年份:
    2007
  • 资助金额:
    $ 55.34万
  • 项目类别:
Molecular Risk Factors for Age-Related Maculopathy
年龄相关性黄斑病的分子危险因素
  • 批准号:
    6659785
  • 财政年份:
    2002
  • 资助金额:
    $ 55.34万
  • 项目类别:
Molecular Risk Factors for Age-Related Maculopathy
年龄相关性黄斑病的分子危险因素
  • 批准号:
    6799179
  • 财政年份:
    2002
  • 资助金额:
    $ 55.34万
  • 项目类别:

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