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Exploring genomic determinants of periodontal disease via shared genetic pathways with cardiovascular disease, diabetes, and bone density

Award Number: K23DE026804
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

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Exploring genomic determinants of periodontal disease via shared genetic pathways with cardiovascular disease, diabetes, and bone density - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Oral Diseases and Disorders Research	000	5	11/29/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Oral Diseases and Disorders Research	000	5	3/16/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $136,629 )
2021	2021	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Oral Diseases and Disorders Research	000	5	8/18/2021	NON-COMPETING CONTINUATION	$136,629
														Subtotal = $136,629

Issue Date FY: 2020 ( Subtotal = $136,629 )
2020	2020	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Oral Diseases and Disorders Research	000	4	8/11/2020	NON-COMPETING CONTINUATION	$136,629
														Subtotal = $136,629

Issue Date FY: 2019 ( Subtotal = $136,634 )
2019	2019	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Oral Diseases and Disorders Research	000	3	7/30/2019	NON-COMPETING CONTINUATION	$136,634
														Subtotal = $136,634

Issue Date FY: 2018 ( Subtotal = $136,634 )
2018	2018	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Oral Diseases and Disorders Research	000	2	8/28/2018	NON-COMPETING CONTINUATION	$136,634
														Subtotal = $136,634

Issue Date FY: 2017 ( Subtotal = $138,634 )
2017	2017	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Oral Diseases and Disorders Research	000	1	9/12/2017	NEW	$138,634
														Subtotal = $138,634

Grand Total All Awards = $685,160

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Exploring genomic determinants of periodontal disease via shared genetic pathways with cardiovascular disease, diabetes, and bone density

Award Number: K23DE026804

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

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