| 1. |
- Divaris, K., et al.
(författare)
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Phenotype Harmonization in the GLIDE2 Oral Health Genomics Consortium
- 2022
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Ingår i: Journal of Dental Research. - : Sage Publications. - 0022-0345 .- 1544-0591. ; 101:11, s. 1408-1416
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Tidskriftsartikel (refereegranskat)abstract
- Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and “precision,” data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface–level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.
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| 2. |
- Divaris, K, et al.
(författare)
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The academic environment: the students' perspective
- 2008
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Ingår i: European journal of dental education : official journal of the Association for Dental Education in Europe. - : Wiley. - 1396-5883. ; 1212 Suppl 1, s. 120-130
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Fries, Niklas, 1991-, et al.
(författare)
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A polygenic score predicts caries experience in elderly Swedish adults
- 2024
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Ingår i: Journal of Dental Research. - : Sage Publications. - 0022-0345 .- 1544-0591. ; 103:5, s. 502-508
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Tidskriftsartikel (refereegranskat)abstract
- Caries is a partially heritable disease, raising the possibility that a polygenic score (PS, a summary of an individual’s genetic propensity for disease) might be a useful tool for risk assessment. To date, PS for some diseases have shown clinical utility, although no PS for caries has been evaluated. The objective of the study was to test whether a PS for caries is associated with disease experience or increment in a cohort of Swedish adults. A genome-wide PS for caries was trained using the results of a published genome-wide association meta-analysis and constructed in an independent cohort of 15,460 Swedish adults. Electronic dental records from the Swedish Quality Registry for Caries and Periodontitis (SKaPa) were used to compute the decayed, missing, and filled tooth surfaces (DMFS) index and the number of remaining teeth. The performance of the PS was evaluated by testing the association between the PS and DMFS at a single dental examination, as well as between the PS and the rate of change in DMFS. Participants in the highest and lowest deciles of PS had a mean DMFS of 63.5 and 46.3, respectively. A regression analysis confirmed this association where a 1 standard deviation increase in PS was associated with approximately 4-unit higher DMFS (P < 2 × 10−16). Participants with the highest decile of PS also had greater change in DMFS during follow-up. Results were robust to sensitivity analysis, which adjusted for age, age squared, sex, and the first 20 genetic principal components. Mediation analysis suggested that tooth loss was a strong mediating factor in the association between PS and DMFS but also supported a direct genetic effect on caries. In this cohort, there are clinically meaningful differences in DMFS between participants with high and low PS for caries. The results highlight the potential role of genomic data in improving caries risk assessment.
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| 4. |
- Heimisdottir, L.H., et al.
(författare)
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Metabolomics Insights in Early Childhood Caries
- 2021
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Ingår i: Journal of Dental Research. - : Sage Publications. - 0022-0345 .- 1544-0591. ; 100:6, s. 615-622
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Tidskriftsartikel (refereegranskat)abstract
- Dental caries is characterized by a dysbiotic shift at the biofilm–tooth surface interface, yet comprehensive biochemical characterizations of the biofilm are scant. We used metabolomics to identify biochemical features of the supragingival biofilm associated with early childhood caries (ECC) prevalence and severity. The study’s analytical sample comprised 289 children ages 3 to 5 (51% with ECC) who attended public preschools in North Carolina and were enrolled in a community-based cross-sectional study of early childhood oral health. Clinical examinations were conducted by calibrated examiners in community locations using International Caries Detection and Classification System (ICDAS) criteria. Supragingival plaque collected from the facial/buccal surfaces of all primary teeth in the upper-left quadrant was analyzed using ultra-performance liquid chromatography–tandem mass spectrometry. Associations between individual metabolites and 18 clinical traits (based on different ECC definitions and sets of tooth surfaces) were quantified using Brownian distance correlations (dCor) and linear regression modeling of log2-transformed values, applying a false discovery rate multiple testing correction. A tree-based pipeline optimization tool (TPOT)–machine learning process was used to identify the best-fitting ECC classification metabolite model. There were 503 named metabolites identified, including microbial, host, and exogenous biochemicals. Most significant ECC-metabolite associations were positive (i.e., upregulations/enrichments). The localized ECC case definition (ICDAS ≥1 caries experience within the surfaces from which plaque was collected) had the strongest correlation with the metabolome (dCor P = 8 × 10−3). Sixteen metabolites were significantly associated with ECC after multiple testing correction, including fucose (P = 3.0 × 10−6) and N-acetylneuraminate (p = 6.8 × 10−6) with higher ECC prevalence, as well as catechin (P = 4.7 × 10−6) and epicatechin (P = 2.9 × 10−6) with lower. Catechin, epicatechin, imidazole propionate, fucose, 9,10-DiHOME, and N-acetylneuraminate were among the top 15 metabolites in terms of ECC classification importance in the automated TPOT model. These supragingival biofilm metabolite findings provide novel insights in ECC biology and can serve as the basis for the development of measures of disease activity or risk assessment.
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| 5. |
- Shungin, Dmitry, et al.
(författare)
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Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Dental caries and periodontitis account for a vast burden of morbidity and healthcare spending, yet their genetic basis remains largely uncharacterized. Here, we identify self-reported dental disease proxies which have similar underlying genetic contributions to clinical disease measures and then combine these in a genome-wide association study meta-analysis, identifying 47 novel and conditionally-independent risk loci for dental caries. We show that the heritability of dental caries is enriched for conserved genomic regions and partially overlapping with a range of complex traits including smoking, education, personality traits and metabolic measures. Using cardio-metabolic traits as an example in Mendelian randomization analysis, we estimate causal relationships and provide evidence suggesting that the processes contributing to dental caries may have undesirable downstream effects on health.
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| 6. |
- Shungin, Dmitry, et al.
(författare)
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Using genetics to test the causal relationship of total adiposity and periodontitis : Mendelian randomization analyses in the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium
- 2015
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 44:2, s. 638-650
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Tidskriftsartikel (refereegranskat)abstract
- Background: The observational relationship between obesity and periodontitis is widely known, yet causal evidence is lacking. Our objective was to investigate causal associations between periodontitis and body mass index (BMI). Methods: We performed Mendelian randomization analyses with BMI-associated loci combined in a genetic risk score (GRS) as the instrument for BMI. All analyses were conducted within the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium in 13 studies from Europe and the USA, including 49 066 participants with clinically assessed (seven studies, 42.1% of participants) and self-reported (six studies, 57.9% of participants) periodontitis and genotype data (17 672/31 394 with/without periodontitis); 68 761 participants with BMI and genotype data; and 57 871 participants (18 881/38 990 with/without periodontitis) with data on BMI and periodontitis. Results: In the observational meta-analysis of all participants, the pooled crude observational odds ratio (OR) for periodontitis was 1.13 [95% confidence interval (CI): 1.03, 1.24] per standard deviation increase of BMI. Controlling for potential confounders attenuated this estimate (OR = 1.08; 95% CI: 1.03, 1.12). For clinically assessed periodontitis, corresponding ORs were 1.25 (95% CI: 1.10, 1.42) and 1.13 (95% CI: 1.10, 1.17), respectively. In the genetic association meta-analysis, the OR for periodontitis was 1.01 (95% CI: 0.99, 1.03) per GRS unit (per one effect allele) in all participants and 1.00 (95% CI: 0.97, 1.03) in participants with clinically assessed periodontitis. The instrumental variable meta-analysis of all participants yielded an OR of 1.05 (95% CI: 0.80, 1.38) per BMI standard deviation, and 0.90 (95% CI: 0.56, 1.46) in participants with clinical data. Conclusions: Our study does not support total adiposity as a causal risk factor for periodontitis, as the point estimate is very close to the null in the causal inference analysis, with wide confidence intervals.
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