Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data.
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ABSTRACT:
SUBMITTER: Shungin D
PROVIDER: S-EPMC6591304 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
Publications
Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data.
Shungin Dmitry D Haworth Simon S Divaris Kimon K Agler Cary S CS Kamatani Yoichiro Y Keun Lee Myoung M Grinde Kelsey K Hindy George G Alaraudanjoki Viivi V Pesonen Paula P Teumer Alexander A Holtfreter Birte B Sakaue Saori S Hirata Jun J Yu Yau-Hua YH Ridker Paul M PM Giulianini Franco F Chasman Daniel I DI Magnusson Patrik K E PKE Sudo Takeaki T Okada Yukinori Y Völker Uwe U Kocher Thomas T Anttonen Vuokko V Laitala Marja-Liisa ML Orho-Melander Marju M Sofer Tamar T Shaffer John R JR Vieira Alexandre A Marazita Mary L ML Kubo Michiaki M Furuichi Yasushi Y North Kari E KE Offenbacher Steve S Ingelsson Erik E Franks Paul W PW Timpson Nicholas J NJ Johansson Ingegerd I
Nature communications 20190624 1
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 ...[more]
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Project description:Hypothesis-free Mendelian randomization studies provide a way to assess the causal relevance of a trait across the human phenome but can be limited by statistical power, sample overlap or complicated by horizontal pleiotropy. The recently described latent causal variable (LCV) approach provides an alternative method for causal inference which might be useful in hypothesis-free experiments across human phenome. We developed an automated pipeline for phenome-wide tests using the LCV approach including steps to estimate partial genetic causality, filter to a meaningful set of estimates, apply correction for multiple testing and then present the findings in a graphical summary termed causal architecture plot. We apply this pipeline to body mass index (BMI) and lipid traits as exemplars of traits where there is strong prior expectation for causal effects, and to dental caries and periodontitis as exemplars of traits where there is a need for causal inference. The results for lipids and BMI suggest that these traits are best viewed as contributing factors on a multitude of traits and conditions, thus providing additional evidence that supports viewing these traits as targets for interventions to improve health. On the other hand, caries and periodontitis are best viewed as a downstream consequence of other traits and diseases rather than a cause of ill health. The automated pipeline is implemented in the Complex-Traits Genetics Virtual Lab ( https://vl.genoma.io ) and results are available in https://view.genoma.io . We propose causal architecture plots based on phenome-wide partial genetic causality estimates as a new way visualizing the overall causal map of the human phenome.
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Project description:Over 90% of adults aged 20 years or older with permanent teeth have suffered from dental caries leading to pain, infection, or even tooth loss. Although caries prevalence has decreased over the past decade, there are still about 23% of dentate adults who have untreated carious lesions in the US. Dental caries is a complex disorder affected by both individual susceptibility and environmental factors. Approximately 35-55% of caries phenotypic variation in the permanent dentition is attributable to genes, though few specific caries genes have been identified. Therefore, we conducted the first genome-wide association study (GWAS) to identify genes affecting susceptibility to caries in adults.Five independent cohorts were included in this study, totaling more than 7000 participants. For each participant, dental caries was assessed and genetic markers (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Due to the heterogeneity among the five cohorts regarding age, genotyping platform, quality of dental caries assessment, and study design, we first conducted genome-wide association (GWA) analyses on each of the five independent cohorts separately. We then performed three meta-analyses to combine results for: (i) the comparatively younger, Appalachian cohorts (N?=?1483) with well-assessed caries phenotype, (ii) the comparatively older, non-Appalachian cohorts (N?=?5960) with inferior caries phenotypes, and (iii) all five cohorts (N?=?7443). Top ranking genetic loci within and across meta-analyses were scrutinized for biologically plausible roles on caries.Different sets of genes were nominated across the three meta-analyses, especially between the younger and older age cohorts. In general, we identified several suggestive loci (P-value???10E-05) within or near genes with plausible biological roles for dental caries, including RPS6KA2 and PTK2B, involved in p38-depenedent MAPK signaling, and RHOU and FZD1, involved in the Wnt signaling cascade. Both of these pathways have been implicated in dental caries. ADMTS3 and ISL1 are involved in tooth development, and TLR2 is involved in immune response to oral pathogens.As the first GWAS for dental caries in adults, this study nominated several novel caries genes for future study, which may lead to better understanding of cariogenesis, and ultimately, to improved disease predictions, prevention, and/or treatment.
| S-EPMC3574042 | biostudies-literature
Project description:BackgroundDental caries is one of the most common chronic diseases and is influenced by a complex interplay of genetic and environmental factors. Most previous genetic studies of caries have focused on identifying genes that contribute to dental caries in specific ethnic groups, usually of European descent.MethodsThe aim of this study is to conduct a genome-wide association study (GWAS) to identify associations affecting susceptibility to caries in a large multiethnic population from Argentina, the Philippines, Guatemala, Hungary, and the USA, originally recruited for studies of orofacial clefts (POFC, N = 3686). Ages of the participants ranged from 2 to 12 years for analysis of the primary dentition, and 18-60 years for analysis of the permanent dentition. For each participant, dental caries was assessed by counts of decayed and filled teeth (dft/DFT) and genetic variants (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Caries was analyzed separately for the primary and permanent dentitions, with age, gender, and presence/absence of any type of OFC treated as covariates. Efficient Mixed-Model Association eXpedited (EMMAX) was used to test genetic association, while simultaneously accounting for relatedness and stratification.ResultsWe identified several suggestive loci (5 × 10-8 < P < 5 × 10-6) within or near genes with plausible biological roles for dental caries, including a cluster of taste receptor genes (TAS2R38, TAS2R3, TAS2R4, TASR25) on chromosome 7 for the permanent dentition analysis, and DLX3 and DLX4 on chromosome 17 for the primary dentition analysis. Genome-wide significant results were seen with SNPs in the primary dentition only; however, none of the identified genes near these variants have known roles in cariogenesis.ConclusionThe results of this study warrant further investigation and may lead to a better understanding of cariogenesis in diverse populations, and help to improve dental caries prediction, prevention, and/or treatment in future.
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Project description: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. Consortium-wide 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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Project description:BackgroundPrevious studies reported varyingly positive, negative, or no relationships between caries and periodontitis. Therefore, the aim was to assess the potential co-occurrence of caries experience and periodontal inflammation on the same teeth.MethodsThis cross-sectional study used data from the Lithuanian National Oral Health Survey. The study included a stratified random sample of 1405 individuals aged 34-78, recruited from 5 Lithuanian cities and 10 peri-urban/rural areas (response rate 52%). Information about sociodemographic (age, sex, education, residence), behavioral (sugar-containing diet, tooth brushing frequency, use of interdental care products, last dental visit, smoking) and biological (systemic disease, use of medication and xerostomia) determinants was collected using the World Health Organization (WHO) Oral Health Questionnaire for Adults supplemented with additional questions. Clinical data were recorded using the WHO criteria and collected by one trained and calibrated examiner. Dental caries status was recorded as sound, decayed, missing, filled surfaces. Subsequently for the analyses, status was recorded at a tooth-level as decayed- and filled-teeth (DT and FT) including proximal, buccal, and oral surfaces. Two measures were used for periodontal status. The probing pocket depth (PPD) was measured at six sites and recorded at a tooth level into the absence of PPD or presence of PPD ≥ 4 mm. Bleeding on probing (BOP) was measured at the same six sites and was recorded as either present or absent at a tooth-level. Univariable and multivariable 2-level random intercept binary logistic regression analyses were utilized.ResultsPositive associations were found between DT and BOP (OR 1.42, 95% CI 1.20-1.67), FT and BOP (OR 2.07, 95% CI 1.82-2.23), DT and PPD (OR 1.38, 95% CI 1.15-1.67) and FT and PPD (OR 2.01, 95% CI 1.83-2.20).ConclusionsOur findings add evidence for the co-occurrence of periodontal inflammation and caries on the same teeth. This suggests the need for increased emphasis on a transdisciplinary approach in designing oral health interventions that target dental caries and periodontal disease simultaneously. In addition, longitudinal studies exploring the co-occurrence of caries and periodontal disease at the same sites, taking into consideration the levels of both conditions and genetic variation, are warranted.
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Project description:BackgroundTooth loss significantly impacts oral function and overall health deterioration. Dental caries and periodontal disease are major contributors to tooth loss, emphasizing the critical need to prevent these conditions. Genetic studies have played a crucial role in deepening our understanding of the underlying mechanisms of these diseases. While large-scale genome-wide association studies (GWAS) on dental caries and periodontal disease have been conducted extensively, research focusing on Asian populations remains limited. Given substantial genetic and lifestyle variations across ethnicities, conducting studies across diverse populations is imperative. This study aimed to uncover new insights into the genetic mechanisms of these diseases, contributing to broader knowledge and potential targeted interventions.MethodsWe conducted a GWAS using genome data from 45,525 Japanese individuals, assessing their self-reported history of dental caries and periodontal disease. Additionally, we performed a meta-analysis by integrating our results with those from a previous large-scale GWAS predominantly involving European populations.ResultsWhile no new loci associated with periodontal disease were identified, we discovered two novel loci associated with dental caries. The lead variants of these loci were intron variant rs10974056 in GLIS3 and intron variant rs4801882 in SIGLEC5.ConclusionOur study findings are anticipated to advance understanding of the underlying mechanisms of dental caries and periodontal disease. Thes insights may inform better management strategies for patients affected by these conditions.
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| S-EPMC10630193 | biostudies-literature
Project description:ObjectivesTo critically examine the methods used for full economic evaluations of preventive interventions for dental caries and periodontitis.MethodsPublished literature post-2000 was searched to April 2021. Based on a developed intervention classification framework for dental caries and periodontitis, only universal, selective or indicated interventions were included in this review. The Drummond 10-point checklist was used for quality appraisal.ResultsOf 3,007 unique records screened for relevance, 73 studies were reviewed. Most model-based studies (61/73) used cost-effectiveness analysis (49%) or cost-benefit analysis (28%). Trial-based studies (16/73) commonly used cost-effectiveness analysis (59%). Four studies used both economic evaluation methods. Sixty-four papers (88%) were on dental caries, eight papers (11%) focused on periodontitis, and one paper (1%) included both oral diseases; 72% of model-based and 82% of trial-based studies were of good quality. The most frequently investigated dental caries preventive interventions were water fluoridation (universal intervention; cost-saving or cost-effective), fissure sealant and fluoride varnish (selective and indicated interventions; cost-effectiveness outcomes were inconsistent). Supportive periodontal therapy with oral health education (indicated intervention; cost-effective) was the most frequently evaluated preventive intervention for periodontitis. Thirty percent of studies with a time horizon > 1 year did not apply an appropriate discount rate and 26% did not comprehensively discuss other important considerations beyond the technical analysis.ConclusionsGeneric health outcome measures should be incorporated for economic evaluations on preventive interventions for dental caries and periodontitis, and an increased focus to prevent periodontitis using economic evaluation methods is needed to inform resource allocation and policy decision-making.
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Project description:Oral Microbiota Analyses of Pediatric Saudi Population Reveals Signatures of Dental Caries
| PRJEB57557 | ENA