Genomic Determinants and Shared Genetic Pathways of Periodontal Disease
| Status: | Recruiting |
|---|---|
| Conditions: | Osteoporosis, Peripheral Vascular Disease, Dental |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Dental / Maxillofacial Surgery, Rheumatology |
| Healthy: | No |
| Age Range: | 45 - 100 |
| Updated: | 9/16/2018 |
| Start Date: | January 30, 2018 |
| End Date: | August 31, 2022 |
| Contact: | Yau-Hua Yu, DDS, DMSc |
| Email: | yau-hua.yu@tufts.edu |
| Phone: | 617-636-6659 |
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 genomewide 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.
of multiple risk factors, little is known about the specific contribution of genetics to PD
pathogenesis. Several genomewide 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 are proposed to refine and validate the PD status in the Women's Health
Study (WHS/WGHS) to improve the phenotypic characterization of GWAS of PD: (1) Addition of
CDC-AAP (Centers for Disease Control - American Academy of Periodontology) periodontal
disease instrument to the WHS annual follow-up survey. (2) Validate existing Periodontal
Disease (PD) status in the WHS/WGHS (subset). Request of dental records for 180 women sampled
from the WHS who had reported diagnosis of PD in the past. (3) Correlation and validation
analysis of new periodontal disease information with requested dental record (most recently
dated). Phone interviews and request of dental records for 180 women sampled from the
WHS/WGHS who visited a dentist within recent 36 months.
In addition, the investigators propose to identify genetic determinants of PD shared with
CVD, DM, or osteoporosis via an integrative computational biological networks approach.
Although the systemic links between PD vs. DM, CVD or osteoporosis have been established in
clinical genetics as well as in experimental models, high-throughput investigations for
gene-gene interplays between the associated conditions (CVD vs. PD; DM vs. PD; osteoporosis
vs. PD) have not been explored yet. The investigators propose to approach this using an
integrative in silico method, combining existing diverse biological information including
genomic, epigenetic, expression and protein data. To our knowledge, this is the first time
that hierarchical levels of integrative precision medicine will be tested for PD vs.
CVD/DM/osteoporosis to generate plausible hypotheses and experimental targets.
Study (WHS/WGHS) to improve the phenotypic characterization of GWAS of PD: (1) Addition of
CDC-AAP (Centers for Disease Control - American Academy of Periodontology) periodontal
disease instrument to the WHS annual follow-up survey. (2) Validate existing Periodontal
Disease (PD) status in the WHS/WGHS (subset). Request of dental records for 180 women sampled
from the WHS who had reported diagnosis of PD in the past. (3) Correlation and validation
analysis of new periodontal disease information with requested dental record (most recently
dated). Phone interviews and request of dental records for 180 women sampled from the
WHS/WGHS who visited a dentist within recent 36 months.
In addition, the investigators propose to identify genetic determinants of PD shared with
CVD, DM, or osteoporosis via an integrative computational biological networks approach.
Although the systemic links between PD vs. DM, CVD or osteoporosis have been established in
clinical genetics as well as in experimental models, high-throughput investigations for
gene-gene interplays between the associated conditions (CVD vs. PD; DM vs. PD; osteoporosis
vs. PD) have not been explored yet. The investigators propose to approach this using an
integrative in silico method, combining existing diverse biological information including
genomic, epigenetic, expression and protein data. To our knowledge, this is the first time
that hierarchical levels of integrative precision medicine will be tested for PD vs.
CVD/DM/osteoporosis to generate plausible hypotheses and experimental targets.
Inclusion Criteria:
- Women who are willing to consent for requesting dental records;
- Outcome 1 - Women who reported periodontal disease diagnosis at any time point up to
the 2006 follow up;
- Outcome 1 - Women whose dental records will be retrievable and usable (retrospectively
2 years and prospectively 1 year at the time of report of periodontal disease
diagnosis)
- Outcome 2 - Women who are willing to complete and turn-in the WHS 2018 Annual
Follow-up Questionnaire with CDC-AAP oral health questions
- Outcome 2 - Women whose dental records will be retrievable and usable (retrospectively
3 years at the time of 2018 Annual Follow-up Questionnaire turn-in)
- The definition of usable dental records consist of but not exclusive to clinical note,
complete periodontal charting, and full-mouth radiographs series (FMX) or panoramic,
bite-wing radiographs that could derive a PD diagnosis based on the American Academy
of Periodontology 1999 definitions.
Exclusion Criteria:
- Women whose dental records are not retrievable or incomplete.
We found this trial at
1
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75 Francis street
Boston, Massachusetts 02115
Boston, Massachusetts 02115
(617) 732-5500
Phone: 617-636-6659
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