Survival genetics methods for detecting sex-dependent genetic effects on Alzheimer’s disease
用于检测阿尔茨海默病性别依赖性遗传效应的生存遗传学方法
基本信息
- 批准号:10670493
- 负责人:
- 金额:$ 38.45万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-15 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AccountingAddressAgeAlzheimer disease preventionAlzheimer&aposs DiseaseAlzheimer&aposs disease riskArchivesCohort StudiesCommunitiesCox ModelsDataData AnalysesDevelopmentDiseaseDisease OutcomeEnvironmental Risk FactorEtiologyFailureGenesGeneticGenetic HeterogeneityGenetic Predisposition to DiseaseGenetic ResearchGenetic studyHazard ModelsHeritabilityHeterogeneityIndividualJointsKnowledgeLate Onset Alzheimer DiseaseLeadLeftLiteratureMeasuresMethodologyMethodsModelingMolecularNeurodegenerative DisordersPhenotypePricePublishingResearchRiskSignal TransductionSpecific qualifier valueStatistical MethodsStudy SubjectSubgroupSurvival AnalysisTestingTimeTwin StudiesVariantaffectionanalytical toolbasebiobankcohortcommunity based participatory researchdata resourcedisease phenotypeepigenetic markergene discoverygene environment interactiongene interactiongenetic architecturegenetic associationgenetic testinggenetic variantgenome-widehigh throughput technologyhuman diseaseimprovedinsightinterestmortality risknovelresearch studyrisk variantsexsuccesssurvival outcometooltraittranscriptomicsuser-friendly
项目摘要
Project Summary
Alzheimer's disease (AD) is a progressive neurodegenerative disease influenced by both genetic
and environmental factors. Although over 50 risk loci with genome-wide significance have been
identified to date, a substantial proportion of AD heritability remains unexplained. With the high-
throughput technologies, a large amount of genetic data has become available for AD genetic
research. While studies utilizing these enriched data resources and considering sex-dependent
genetic effects, joint effects of multiple markers, and AD risk information (e.g., time-to-AD
phenotype) hold great promise for novel AD gene discovery, rigorous analytical tools for such
analysis are still lacking. Most of the statistical tools can't account for genetic heterogeneity.
Besides, existing multi-marker survival tests are largely based on the Cox model for covariate
adjustment. Mis-specifying the covariate-adjustment model could lead to spurious association
findings. Furthermore, time to AD is usually interval censored in cohort studies and subject to the
competing risk of death, but no multi-marker survival test is currently available to handle interval
censored competing risks data. To address the limitations of existing methods and facilitate
genetic association analysis of time-to-AD outcomes considering sex-related genetic
heterogeneity, we will develop three multi-marker survival tests based on the additive hazards
model, the accelerated failure time model, and interval censored survival traits, respectively. We
will further extend these three tests for gene-gene/gene-environment interaction analyses. All the
new tests can deal with left truncation and competing risks, two common issues in time-to-AD
analyses. The new methods will be programmed into R packages to be disseminated through the
Comprehensive R Archive Network. Additionally, we will apply the methods to the UK Biobank
and ROSMAP data to search for AD-associated genes and test for gene-sex interactions. The
successful completion of this project will address analytic challenges faced by the ongoing AD
genetic research, and advance the statistical methodology development for genetic association
analysis of survival outcomes in general. The application of the new methods to the UK Biobank
and ROSMAP data will provide new insights into the genetic architecture of AD, especially the
sex-specific genetic etiology.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Chenxi Li其他文献
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{{ truncateString('Chenxi Li', 18)}}的其他基金
Efficient methods for genome-wide survival analysis of early childhood caries
儿童早期龋齿全基因组生存分析的有效方法
- 批准号:
10696112 - 财政年份:2022
- 资助金额:
$ 38.45万 - 项目类别:
Efficient methods for genome-wide survival analysis of early childhood caries
儿童早期龋齿全基因组生存分析的有效方法
- 批准号:
10571345 - 财政年份:2022
- 资助金额:
$ 38.45万 - 项目类别:
Survival genetics methods for genetic association studies of early childhood caries
用于早期儿童龋齿遗传关联研究的生存遗传学方法
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10453481 - 财政年份:2021
- 资助金额:
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Analysis of Complex Caries Life Course Data in Inner City African-American Childr
内城非裔美国儿童复杂龋病生命历程数据分析
- 批准号:
8772028 - 财政年份:2014
- 资助金额:
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