| 1. |
- Dodhia, Serena A., et al.
(författare)
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Examining the causal association between 25-hydroxyvitamin D and caries in children and adults : A two-sample Mendelian randomization approach
- 2021
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Ingår i: Wellcome Open Research. - : F1000 Research Ltd. - 2398-502X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prior observational studies have reported that higher levels of vitamin D are associated with decreased caries risk in children. However, these studies are prone to bias and confounding so do not provide causal inference. Genetic variants associated with a risk factor of interest can be used as proxies, in a Mendelian randomization (MR) analysis, to test for causal association with an outcome. The objective was to estimate the causal association between serum 25-hydroxyvitamin D (25(OH)D) (the commonly measured vitamin D metabolite in blood) and dental caries using a two-sample MR approach which estimates the causal effect of an exposure on an outcome.Methods: A total of 79 genetic variants reliably associated with 25(OH)D were identified from genome-wide association studies and used as a proxy measure of 25(OH)D. The association of this proxy measure with three outcome measures was tested; specifically: caries in primary teeth (n=17,035, aged 3-12 years), caries in permanent teeth in childhood and adolescence (n=13,386, aged 6-18 years), and caries severity in adulthood proxied by decayed, missing and filled tooth surfaces (DMFS) counts (n=26,792, aged 18-93 years).Results: The estimated causal effect of a one standard deviation increase in natural log-transformed 25(OH)D could be summarized as an odds ratio of 1.06 (95%CI: 0.81, 1.31; P=0.66) for caries in primary teeth and 1.00 (95%CI: 0.76, 1.23; P=0.97) for caries in permanent teeth in childhood and adolescence. In adults, the estimated casual effect of a one standard deviation increase in natural log-transformed 25(OH)D was 0.31 fewer affected tooth surfaces (95%CI: from 1.81 fewer DMFS to 1.19 more DMFS; P=0.68)Conclusions: The MR-derived effect estimates for these three measures are small in magnitude with wide confidence intervals and do not provide evidence for a causal relationship between 25(OH)D and dental caries.
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| 2. |
- Dudding, Tom, et al.
(författare)
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Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci
- 2019
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Mouth ulcers are the most common ulcerative condition and encompass several clinical diagnoses, including recurrent aphthous stomatitis (RAS). Despite previous evidence for heritability, it is not clear which specific genetic loci are implicated in RAS. In this genome-wide association study (n = 461,106) heritability is estimated at 8.2% (95% CI: 6.4%, 9.9%). This study finds 97 variants which alter the odds of developing non-specific mouth ulcers and replicate these in an independent cohort (n = 355,744) (lead variant after meta-analysis: rs76830965, near IL12A, OR 0.72 (95% CI: 0.71, 0.73); P = 4.4e-483). Additional effect estimates from three independent cohorts with more specific phenotyping and specific study characteristics support many of these findings. In silico functional analyses provide evidence for a role of T cell regulation in the aetiology of mouth ulcers. These results provide novel insight into the pathogenesis of a common, important condition.
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| 3. |
- Eriksson, Linda, et al.
(författare)
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Allelic Variation in Taste Genes Is Associated with Taste and Diet Preferences and Dental Caries
- 2019
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Taste and diet preferences are complex and influenced by both environmental and host traits while affecting both food selection and associated health outcomes. The present study genotyped 94 single nucleotide polymorphisms (SNPs) in previously reported taste and food intake related genes and assessed associations with taste threshold (TT) and preferred intensity (PT) of sweet, sour and bitter, food preferences, habitual diet intake, and caries status in healthy young Swedish men and women (n = 127). Polymorphisms in the GNAT3, SLC2A4, TAS1R1 and TAS1R2 genes were associated with variation in TT and PT for sweet taste as well as sweet food intake. Increasing PT for sweet was associated with increasing preference and intake of sugary foods. Similarly, increasing TT for sour was associated with increasing intake of sour foods, whereas the associations between food preference/intake and TT/PT for bitter was weak in this study group. Finally, allelic variation in the GNAT3, SLC2A2, SLC2A4, TAS1R1 and TAS1R2 genes was associated with caries status, whereas TT, PT and food preferences were not. It was concluded that variations in taste receptor, glucose transporter and gustducin encoding genes are related to taste perception, food preference and intake as well as the sugar-dependent caries disease.
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| 4. |
- Esberg, Anders, et al.
(författare)
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Heritability of Oral Microbiota and Immune Responses to Oral Bacteria
- 2020
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Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Maintaining a symbiotic oral microbiota is essential for oral and dental health, and host genetic factors may affect the composition or function of the oral microbiota through a range of possible mechanisms, including immune pathways. The study included 836 Swedish twins divided into separate groups of adolescents (n= 418) and unrelated adults (n= 418). Oral microbiota composition and functions of non-enzymatically lysed oral bacteria samples were evaluated using 16S rRNA gene sequencing and functional bioinformatics tools in the adolescents. Adaptive immune responses were assessed by testing for serum IgG antibodies against a panel of common oral bacteria in adults. In the adolescents, host genetic factors were associated with both the detection and abundance of microbial species, but with considerable variation between species. Host genetic factors were associated with predicted microbiota functions, including several functions related to bacterial sucrose, fructose, and carbohydrate metabolism. In adults, genetic factors were associated with serum antibodies against oral bacteria. In conclusion, host genetic factors affect the composition of the oral microbiota at a species level, and host-governed adaptive immune responses, and also affect the concerted functions of the oral microbiota as a whole. This may help explain why some people are genetically predisposed to the major dental diseases of caries and periodontitis.
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| 5. |
- Esberg, Anders, et al.
(författare)
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Oral Microbiota Profile Associates with Sugar Intake and Taste Preference Genes
- 2020
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Oral microbiota ecology is influenced by environmental and host conditions, but few studies have evaluated associations between untargeted measures of the entire oral microbiome and potentially relevant environmental and host factors. This study aimed to identify salivary microbiota cluster groups using hierarchical cluster analyses (Wards method) based on 16S rRNA gene amplicon sequencing, and identify lifestyle and host factors which were associated with these groups. Group members (n = 175) were distinctly separated by microbiota profiles and differed in reported sucrose intake and allelic variation in the taste-preference-associated genes TAS1R1 (rs731024) and GNAT3 (rs2074673). Groups with higher sucrose intake were either characterized by a wide panel of species or phylotypes with fewer aciduric species, or by a narrower profile that included documented aciduric- and caries-associated species. The inferred functional profiles of the latter type were dominated by metabolic pathways associated with the carbohydrate metabolism with enrichment of glycosidase functions. In conclusion, this study supported in vivo associations between sugar intake and oral microbiota ecology, but it also found evidence for a variable microbiota response to sugar, highlighting the importance of modifying host factors and microbes beyond the commonly targeted acidogenic and acid-tolerant species. The results should be confirmed under controlled settings with comprehensive phenotypic and genotypic data.
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| 6. |
- Esberg, Anders, et al.
(författare)
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Using Oral Microbiota Data to Design a Short Sucrose Intake Index
- 2021
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Excessive sucrose consumption is associated with numerous health problems, including dental caries, and is considered to play a critical role in shaping the human microbiota. Here, we aimed to confirm the association between sucrose exposure and oral microbiota profile, develop a short food-based index capturing variation among sucrose consumers and validate it against oral microbiota and dental caries in a derivation cohort with 16- to 79-year-old participants (n = 427). Intake and food preferences were recorded by questionnaires and saliva microbiota by 16S rDNA sequencing. Taxonomic similarities clustered participants into five clusters, where one stood out with highest sucrose intake and predicted sugar related metabolic pathways but lowest species diversity in the microbiota. Multivariate modelling of food intake and preferences revealed foods suitable for a sucrose index. This, similarly to sucrose intake, was related to bacterial pattern and caries status. The validity of the sucrose index was replicated in the population-based Gene-Lifestyle Interactions in Dental Endpoints (GLIDE, n = 105,520 Swedish adults) cohort. This suggested that the index captured clinically relevant variation in sucrose intake and that FFQ derived information may be suitable for screening of sucrose intake in the clinic and epidemiological studies, although adjustments to local consumption habits are needed.
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| 7. |
- Frazier-Wood, Alexis C., et al.
(författare)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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| 8. |
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| 9. |
- Gormley, Alexander, et al.
(författare)
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Subtypes of early childhood caries predict future caries experience
- 2023
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Ingår i: Community Dentistry and Oral Epidemiology. - : John Wiley & Sons. - 0301-5661 .- 1600-0528. ; 51:5, s. 966-975
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To test whether postulated subtypes of early childhood caries (ECC) are predictive of subsequent caries experience in a population-based cohort of Swedish children.Methods: The study included children aged between 3 and 5 years at study entry with dental records available for at least 5 years of follow-up. Dental record data were retrieved from the Swedish Quality Registry for Caries and Periodontal disease (SKaPa) for the initial and follow-up visits. Participants who had ECC at study entry were assigned to one of five ECC subtypes (termed classes 1-5) using latent class modelling of tooth surface-level caries experience. Subsequent experience of caries was assessed using the decayed, missing and filled surfaces indices (dmfs/DMFS) at follow-up visits, and compared between ECC subtypes using logistic and negative binomial regression modelling.Results: The study included 128 355 children who had 3 or more dental visits spanning at least 5 years post-baseline. Of these children, 31 919 had caries at the initial visit. Baseline ECC subtype was associated with differences in subsequent disease experience. As an example, 83% of children who had a severe form of ECC at age 5 went on to have caries in the permanent dentition by the end of the study, compared to 51% of children who were caries-free at age 5 (adjusted odds ratio of 4.9 for new disease at their third follow-up).Conclusion: ECC subtypes assigned at a baseline visit are associated with differences in subsequent caries experience in both primary and permanent teeth. This suggests that the development and future validation of an ECC classification can be used in addition to current prediction tools to help identify children at high risk of developing new caries lesions throughout childhood and adolescence.
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| 10. |
- Hallang, Shirleen, et al.
(författare)
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Healthy oral lifestyle behaviours are associated with favourable composition and function of the oral microbiota
- 2021
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Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Modifiable lifestyle interventions may influence dental disease by shifting the composition of the oral microbiota. This study aimed to test whether lifestyle traits are associated with oral microbiota composition and function. Swedish volunteers, aged 16 to 79 years, completed a lifestyle traits questionnaire including lifestyle characteristics and oral health behaviours. Bacterial 16S rDNA amplicons were sequenced and classified into genera and species, using salivary DNA. Microbiota functions were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States and the KO Database of Molecular Functions by ortholog annotation. Tests for association used partial least squares and linear regression analysis with correction for multiple testing. The main analysis included 401 participants and 229 common bacterial species (found in ≥10% of the participants). The overall microbiota composition was strongly associated with questions “do you think caries is a disease?” and “do you use floss or a toothpick?”. Enriched relative abundance of Actinomyces, Campylobacter, Dialister, Fusobacterium, Peptidophaga and Scardovia genera (all p < 0.05 after adjustment for multiple testing), and functional profiles showing enrichment of carbohydrate related functions, were found in participants who answered “no” to these questions. Socio-demographic traits and other oral hygiene behaviours were also associated. Healthier oral microbiota composition and predicted functions are found in those with favourable oral health behaviours. Modifiable risk factors could be prioritized for possible interventions.
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