Trans-omics elucidation of genetic architecture underlying cardiovascular and HLBS diseases
Trans-omics elucidation of genetic architecture underlying cardiovascular and HLBS diseases
批准号:
9895848
负责人:
Charles L Kooperberg
金额:
$52.95万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-05-01 至 2022-04-30
关键词:
AffectAreaBiologicalBiological ProcessBloodCardiovascular Diagnostic TechniquesCardiovascular DiseasesChronicClinicalClinical ResearchCollaborationsComb animal structureComplementComplexCoronary heart diseaseCorrelation StudiesDataDiagnosticDiseaseEpidemiologyEpigenetic ProcessEthnic OriginEventFred Hutchinson Cancer Research CenterGene ExpressionGenesGeneticGenetic DiseasesGenetic ResearchGenetic TranscriptionGenetic VariationGenomeGenotypeHeartHeart DiseasesHematological DiseaseHuman BiologyIndividualKnowledgeLightLinkLungLung diseasesMapsMeasuresMethylationMinorityModelingMolecularMolecular ProfilingMorbidity - disease rateMultiomic DataPathogenesisPhasePhenotypePopulationProteinsProteomePublic HealthRNARaceResearchResearch PersonnelResourcesRiskRisk FactorsSleepSleep DisordersStrokeTechnologyTestingTissuesTrans-Omics for Precision MedicineUniversitiesUntranslated RNAVariantVenousbaseburden of illnesscardiovascular disorder epidemiologycardiovascular disorder riskcardiovascular risk factorclinical phenotypeclinical practicecohortdisease phenotypedisorder riskdisorder subtypedrug developmentexperiencegene interactiongenetic architecturegenetic epidemiologygenetic variantgenome wide association studygenome-widegenomic epidemiologygenomic locushealth practiceinsightmetabolomemethylomeminority healthmolecular phenotypemortalitymultiple omicsnovelphenotypic biomarkerpleiotropismpolygenic risk scoreprecision medicinepredictive signatureprogramsprotein expressionprotein metabolitestatisticstool developmenttraittranscriptometranscriptomicswhole genome
中文摘要
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英文摘要
Abstract
Large-scale genome-wide association studies (GWAS), through genotyping or sequencing, have identified
thousands of loci that appear to influence complex traits and diseases. A fundamental limitation of this
approach, however, is that it reveals statistical correlation between the genotype at a variant and the
phenotype, but does not identify functional variants. With a few exceptions, the precise functional variants in
non-coding regions remain unknown, much less the mechanism through which these variants affect
phenotype. Few strategies are currently available for systematically delineating the molecular events that
connect genetic variants to phenotype. This proposal builds upon an existing collaboration between
researchers in statistics, genomics and cardiovascular epidemiology at Stanford University and Fred
Hutchinson Cancer Research Center. Leveraging the unique multi-omics resources generated by Trans
Omics for Precision Medicine (TOPMed) program, the objective of this application is to implement and apply
analytic strategies for elucidating the genetic basis and molecular mechanisms underlying chronic
conditions related to heart, lung, blood and sleep. Using cardiovascular diseases (CVD) as an entry point,
which has become a leading cause of morbidity and mortality worldwide, the three Specific Aims are (1) to
identify genetic-, epigenetic-, RNA-, protein- and metabolite-based disease risk factors relevant to minority
populations, and to construct polygenic disease risk scores for minority individuals; (2) to identify epistatic
interaction of disease risk; and (3) to construct multi-omics molecular signatures that predict disease risk as
well as define disease subtypes. Our rationale is that each type of omics data offers a quantitative
intermediate phenotype linking the genome and the disease phenotype; hence jointly modeling multiple
omics data may enable us to reconstruct key biological processes related to disease pathogenesis. Our
proposed framework is generally applicable, and offers an efficient and principled strategy to probe into the
genetic basis of complex diseases. Successful completion of this research will contribute to human biology,
minority health and clinical practice.
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科研奖励(0)
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批准号:8571986
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资助金额:$57.42万
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资助金额:$35.2万
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依托单位:
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批准号:8452714
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