Exploring genomic determinants of periodontal disease via shared genetic pathways with cardiovascular disease, diabetes, and bone density
通过与心血管疾病、糖尿病和骨密度共享的遗传途径探索牙周病的基因组决定因素
基本信息
- 批准号:9451794
- 负责人:
- 金额:$ 13.86万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-13 至 2022-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcademyAdultAdvisory CommitteesAffectAmericanApplications GrantsAreaBioinformaticsBiologicalBone DensityCardiovascular DiseasesCatalogsCaucasiansCenters for Disease Control and Prevention (U.S.)ClinicalClinical ResearchCohort StudiesCollaborationsComorbidityComplexDataData CollectionData SetDatabasesDentalDental RecordsDentistsDevelopmentDiabetes MellitusDiseaseEnrollmentEpidemiologyFamily history ofFramingham Heart StudyFundingFutureGenesGeneticGenetic DeterminismGenomeGenomicsGoalsHealthIncidenceInterviewInvestigationKnowledgeLearningLinkLiteratureMentorsMentorshipMeta-AnalysisMolecular ProfilingMyocardial InfarctionNational Health and Nutrition Examination SurveyOsteoporosisOutcomeParticipantPathogenesisPathway AnalysisPathway interactionsPatient Self-ReportPatientsPeriodontal Attachment LossPeriodontal DiseasesPeriodontitisPhenotypePhonationPopulationProteinsPublishingReportingResearchResearch DesignResearch PersonnelResearch ProposalsResourcesRiskRisk FactorsSamplingScientistSiteSmokeSurveysTalentsTelephoneTrainingTwin StudiesUpdateValidationVariantVeteransWomanWomen&aposs HealthWorkbasecareerdatabase of Genotypes and Phenotypesdisease diagnosisepidemiology studyepigenetic regulationexperienceexperimental studyfollow-upgenetic epidemiologygenome databasegenome wide association studygenome-widehigh dimensionalityprecision medicineprogramsskillssocialtraitvalidation studieswhole genome
项目摘要
Despite significant improvement in treating periodontal disease (PD) and the identification of multiple
risk factors, little is known about the specific contribution of genetics to PD pathogenesis. Several genome-
wide association studies (GWAS) of PD have been published, but only one reported locus has reached the
threshold for genome-wide significance. Epidemiological studies and biological experiments established
associations and suggested common pathogenetic pathways between PD and cardiovascular disease (CVD),
diabetes (DM), and osteoporosis. The overall objective is to identify genetic loci for PD as a first step toward
a better understanding of PD pathogenesis. In a preliminary study in the Women's Genome Health Study
(WGHS), new-onset cases of PD were associated with a family history of myocardial infarction (MI). Further
preliminary analyses presented shared phenotypic variation of PD/CVD, PD/DM, or PD/osteoporosis that
could be accounted by the whole-genome genetic matrices. Several variants from the GWAS catalog of bone
density and family history of MI were found correlated with PD in the WGHS. Based on these findings and the
literature, the central hypothesis is that there are common pathogenetic links between PD and these other
diseases and that GWAS using the comorbidity case definitions will help identify potential common loci. Three
specific aims independently refine the approach to GWAS of PD: (1) Validate and expand the PD information
by adding the CDC-AAP self-reported periodontal parameters to the annual follow-up survey in the Women's
Health Study; (2) Identify genetic determinants of PD shared with CVD, DM, or osteoporosis via an integrative
computational biological networks approach; and (3) Preparatory training to connect and collaborate with future
large dental-genomic databases for GWAS of PD.
These aims also provide a mentored training experience for Dr. Yau-Hua Yu, a talented dentist scientist
with a strong background in periodontology and bioinformatics. Dr. Yu's career goal is to integrate
epidemiological, genomic and clinical studies to elucidate the systemic links and genetic components that
periodontal disease shares with cardiovascular disease, diabetes and osteoporosis. Given the administrative
and analytical complexity of this intended research path, her training goal is to acquire skills and experience in
the following areas: 1) Data collection, analysis, interpretation and validation studies for self-reported
outcomes. 2) Management, quantitative analysis and interpretation of large-scale genetic epidemiological
datasets across multiple sites and technological platforms. 3) Accession, integration and interpretation of high-
dimensional data-rich bioinformatics resources to enrich prior and develop new hypotheses. Dr. Yu and her
mentor, Dr. Bjorn Steffensen, have assembled a team of advisors who are experts in their fields as well as
leaders of the large cohort studies required for the proposed work. The proposed work will highlight future
research paths for PD and open possible new avenues of investigation for comorbid conditions.
项目成果
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Yau-Hua Yu其他文献
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