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Sökning: WFRF:(Haworth Simon)

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1.
  • Esberg, A., et al. (författare)
  • Carbonic Anhydrase 6 Gene Variation influences Oral Microbiota Composition and Caries Risk in Swedish adolescents
  • 2019
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Carbonic anhydrase VI (CA6) catalyses the reversible hydration of carbon dioxide in saliva with possible pH regulation, taste perception, and tooth formation effects. This study assessed effects of variation in the CA6 gene on oral microbiota and specifically the acidophilic and caries-associated Streptococcus mutans in 17-year old Swedish adolescents (n = 154). Associations with caries status and secreted CA6 protein were also evaluated. Single Nucleotide Polymorphisms (27 SNPs in 5 haploblocks) and saliva and tooth biofilm microbiota from Illumina MiSeq 16S rDNA (V3-V4) sequencing and culturing were analysed. Haploblock 4 (rs10864376, rs3737665, rs12138897) CCC associated with low prevalence of S. mutans (OR (95% CI): 0.5 (0.3, 0.8)), and caries (OR 0.6 (0.3, 0.9)), whereas haploblock 4 TTG associated with high prevalence of S. mutans (OR: 2.7 (1.2, 5.9)) and caries (OR: 2.3 (1.2, 4.4)). The TTG-haploblock 4 (represented by rs12138897(G)) was characterized by S. mutans, Scardovia wiggsiae, Treponema sp. HOT268, Tannerella sp. HOT286, Veillonella gp.1 compared with the CCC-haploblock 4 (represented by rs12138897(C)). Secreted CA6 in saliva was weakly linked to CA6 gene variation. In conclusion, the results indicate that CA6 gene polymorphisms influence S. mutans colonization, tooth biofilm microbiota composition and risk of dental caries in Swedish adolescents.
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2.
  • Esberg, Anders, et al. (författare)
  • Heritability of Oral Microbiota and Immune Responses to Oral Bacteria
  • 2020
  • Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 8:8
  • 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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3.
  • Haworth, Simon, et al. (författare)
  • Using national register data to estimate the heritability of periodontitis
  • 2021
  • Ingår i: Journal of Clinical Periodontology. - : John Wiley & Sons. - 0303-6979 .- 1600-051X. ; 48:6, s. 756-764
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To identify whether periodontal traits derived from electronic dental records are biologically informative and heritable.Materials and methods: The study included 11,974 adult twins (aged 30–92 years) in the Swedish Twin Registry. Periodontal records from dental examinations were retrieved from a national register and used to derive continuous measures of periodontal health. A latent class approach was used to derive categorial measures of periodontal status. The correlation patterns in these traits were contrasted in monozygotic and dizygotic twin pairs using quantitative genetic models to estimate the heritability of the traits.Results: For continuous traits, heritability estimates ranged between 41.5% and 48.3% with the highest estimates for number of missing tooth surfaces and rate of change in number of deep periodontal pockets (≥6 mm). For categorial traits, the latent class approach identified three classes (good periodontal health, mild periodontitis signs and severe signs of periodontitis) and there was a clear difference in the hazard for subsequent tooth loss between these three classes. Despite this, the class allocations were only slightly more heritable than a conventional dichotomous disease definition (45.2% vs. 42.6%).Conclusions: Periodontitis is a moderately heritable disease. Quantitative periodontal traits derived from electronic records are an attractive target for future genetic association studies.
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4.
  • Manousaki, D., et al. (författare)
  • Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis
  • 2017
  • Ingår i: American Journal of Human Genetics. - : CELL PRESS. - 0002-9297 .- 1537-6605. ; 101:2, s. 227-238
  • Tidskriftsartikel (refereegranskat)abstract
    • Vitamin D insufficiency is common, correctable, and influenced by genetic factors, and it has been associated with risk of several diseases. We sought to identify low-frequency genetic variants that strongly increase the risk of vitamin D insufficiency and tested their effect on risk of multiple sclerosis, a disease influenced by low vitamin D concentrations. We used whole-genome sequencing data from 2,619 individuals through the UK10K program and deep-imputation data from 39,655 individuals genotyped genome-wide. Meta-analysis of the summary statistics from 19 cohorts identified in CYP2R1 the low-frequency (minor allele frequency = 2.5%) synonymous coding variant g.14900931G>A (p.Asp120Asp) (rs117913124[A]), which conferred a large effect on 25-hydroxyvitamin D (25OHD) levels (-0.43 SD of standardized natural log-transformed 25OHD per A allele; p value = 1.5 x 10(-88)). The effect on 25OHD was four times larger and independent of the effect of a previously described common variant near CYP2R1. By analyzing 8,711 individuals, we showed that heterozygote carriers of this low-frequency variant have an increased risk of vitamin D insufficiency (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.78-2.78, p = 1.26 3 10 x(-12)). Individuals carrying one copy of this variant also had increased odds of multiple sclerosis (OR = 1.4, 95% CI = 1.19-1.64, p = 2.63 3 10 x(-5)) in a sample of 5,927 case and 5,599 control subjects. In conclusion, we describe a low-frequency CYP2R1 coding variant that exerts the largest effect upon 25OHD levels identified to date in the general European population and implicates vitamin D in the etiology of multiple sclerosis.
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5.
  • Shungin, Dmitry, et al. (författare)
  • Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data
  • 2019
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 10:1
  • 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.
  • Dodhia, Serena A., et al. (författare)
  • Examining the causal association between 25-hydroxyvitamin D and caries in children and adults : A two-sample Mendelian randomization approach
  • 2021
  • Ingår i: Wellcome Open Research. - : F1000 Research Ltd. - 2398-502X. ; 5
  • 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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7.
  • Dudding, Tom, et al. (författare)
  • Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci
  • 2019
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 10
  • 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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8.
  • Eriksson, Linda, et al. (författare)
  • Allelic Variation in Taste Genes Is Associated with Taste and Diet Preferences and Dental Caries
  • 2019
  • Ingår i: Nutrients. - : MDPI. - 2072-6643 .- 2072-6643. ; 11:7
  • 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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9.
  • Esberg, Anders, et al. (författare)
  • Oral Microbiota Profile Associates with Sugar Intake and Taste Preference Genes
  • 2020
  • Ingår i: Nutrients. - : MDPI. - 2072-6643 .- 2072-6643. ; 12:3
  • 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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10.
  • Esberg, Anders, et al. (författare)
  • Using Oral Microbiota Data to Design a Short Sucrose Intake Index
  • 2021
  • Ingår i: Nutrients. - 2072-6643 .- 2072-6643. ; 13:5
  • 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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