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:
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.
尽管在治疗牙周疾病(PD)方面有显着改善和多种鉴定
风险因素对遗传学对PD发病机理的特定贡献知之甚少。几个基因组 -
PD的广泛关联研究(GWAS)已发表,但只有一个报道的基因座达到了
全基因组意义的阈值。建立的流行病学研究和生物学实验
关联并提出了PD和心血管疾病(CVD)之间的常见致病途径,
糖尿病(DM)和骨质疏松症。总体目标是将PD的遗传基因识别为迈向的第一步
更好地了解PD发病机理。在女性基因组健康研究的初步研究中
(WGHS),新发的PD病例与心肌梗塞(MI)的家族史有关。更远
初步分析提出了PD/CVD,PD/DM或PD/骨质疏松症的共享表型变化
可以通过全基因组遗传基质来解释。 GWAS骨骼目录中的几种变体
发现MI的密度和家族史与WGHS中的PD相关。基于这些发现和
文献,中心假设是PD与其他这些之间存在常见的致病联系
疾病和使用合并症案例定义的GWAS将有助于识别潜在的常见基因座。三
特定目标独立完善了PD GWA的方法:(1)验证和扩展PD信息
通过将CDC-AAP自我报告的牙周参数添加到妇女的年度随访调查中
健康研究; (2)通过综合性确定与CVD,DM或骨质疏松症共享的PD的遗传决定因素
计算生物网络方法; (3)与未来建立联系和合作的准备培训
PD GWA的大型牙科数据库。
这些目标还为才华横溢的牙医科学家Yau-Hua Yu博士提供了指导的培训经验
具有牙周病学和生物信息学方面的良好背景。 Yu博士的职业目标是整合
流行病学,基因组和临床研究,以阐明全身联系和遗传成分
牙周疾病与心血管疾病,糖尿病和骨质疏松症具有共同点。给定管理
以及这一预期研究路径的分析复杂性,她的培训目标是获得技能和经验
以下领域:1)自我报告的数据收集,分析,解释和验证研究
结果。 2)管理,定量分析和大规模遗传流行病学的解释
跨多个站点和技术平台的数据集。 3)高位的加入,整合和解释
尺寸丰富的生物信息学资源以丰富先验和发展新的假设。 Yu博士和她
导师比约恩·斯特芬森(Bjorn Steffensen)博士召集了一组顾问团队,这些顾问是其领域的专家
拟议工作需要大型队列研究的领导者。拟议的工作将突出未来
PD的研究路径和开放可能的合并条件调查的新途径。
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)

暂无数据
数据更新时间:2024-06-01
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