| 1. |
- Haworth, Simon, et al.
(författare)
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Consortium-based genome-wide meta-analysis for childhood dental caries traits
- 2018
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 27:17, s. 3113-3127
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Tidskriftsartikel (refereegranskat)abstract
- Prior studies suggest dental caries traits in children and adolescents are partially heritable, but there has been no large-scale consortium genome-wide association study (GWAS) to date. We therefore performed GWAS for caries in participants aged 2.5-18.0 years from nine contributing centres. Phenotype definitions were created for the presence or absence of treated or untreated caries, stratified by primary and permanent dentition. All studies tested for association between caries and genotype dosage and the results were combined using fixed-effects meta-analysis. Analysis included up to 19 003 individuals (7530 affected) for primary teeth and 13 353 individuals (5875 affected) for permanent teeth. Evidence for association with caries status was observed at rs1594318-C for primary teeth [intronic within ALLC, odds ratio (OR) 0.85, effect allele frequency (EAF) 0.60, P 4.13e-8] and rs7738851-A (intronic within NEDD9, OR 1.28, EAF 0.85, P 1.63e-8) for permanent teeth. Consortiumwide estimated heritability of caries was low [h2 of 1% (95% CI: 0%: 7%) and 6% (95% CI 0%: 13%) for primary and permanent dentitions, respectively] compared with corresponding within-study estimates [h2 of 28% (95% CI: 9%: 48%) and 17% (95% CI: 2%: 31%)] or previously published estimates. This study was designed to identify common genetic variants with modest effects which are consistent across different populations. We found few single variants associated with caries status under these assumptions. Phenotypic heterogeneity between cohorts and limited statistical power will have contributed; these findings could also reflect complexity not captured by our study design, such as genetic effects which are conditional on environmental exposure.
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| 2. |
- Haworth, Simon, et al.
(författare)
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Tooth loss is a complex measure of oral disease : determinants and methodological considerations
- 2018
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Ingår i: Community Dentistry and Oral Epidemiology. - : John Wiley & Sons. - 0301-5661 .- 1600-0528. ; 46:6, s. 555-562
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Counts of missing teeth or measures of incident tooth loss are gaining attention as a simple way to measure dental status in large population studies. We explore the meaning of these metrics and how missing teeth might influence other measures of dental status.METHODS: An observational study was performed in 2 contrasting adult populations. In total, 62 522 adult participants were available with clinically assessed caries and periodontal indices from the Swedish arm of the Gene-Lifestyle Interactions and Dental Endpoints Study (GLIDE) and the Korea National Health and Nutrition Examination Survey (KNHANES) in the Republic of Korea. Longitudinal measures of tooth loss were available for 28 244 participants in GLIDE with median follow-up of 10.6 years.RESULTS: In longitudinal analysis, hazard for tooth loss was associated with baseline dental status (previous tooth loss, periodontal status and caries status) and socio-demographic variables (age, smoking status and highest educational level). Analysis of cross-sectional data suggested that indices of caries exposure were not independent of periodontal status. The strength and direction of association varied between groups, even for measures specifically intended to avoid measuring tooth loss. Individuals with impaired periodontal health (community periodontal index [CPI] 3 or higher in any sextant) had higher standardized decayed and filled surfaces (DFS; number of DFS divided by total number of tooth surfaces) in GLIDE (incidence risk ratio [IRR] 1.05 [95% CI: 1.04, 1.07], but lower standardized DFS in KNHANES (IRR: 0.95 [0.92, 0.98]) than individuals with better periodontal health (CPI <3 in all sextants).CONCLUSIONS: Incident tooth loss is a complex measure of dental disease, with multiple determinants. The relative importance of dental caries and periodontal disease as drivers of tooth loss differs between age groups. Measures of dental caries exposure are associated with periodontal status in the studied populations, and these associations can be population-specific. Consideration of the study-specific properties of these metrics may be required for valid inference in large population studies.
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| 3. |
- 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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