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Title [sv]
Kunskap om karies genom populationsgenetik och mikrobiotakarakterisering ? GLIDE konsortiet
Title [en]
Understanding dental caries through genetics and mircobiota characterization - the GLIDE consortium
Abstract [en]
Dental caries is a complex disease, and like other such diseases it manifests through complex interactions of genetic and environmental risk factors. The present project aims at understanding dental caries using genetics and environmental exposures separately and in interaction. Specifically, we will search (i) genetic risk factors for dental caries, (ii) associations with lifestyle and cardiovascular risk factors and evaluate causality between BMI and dental caries using genotypes as instrumental variables, and (iii) associations between taste genes (sweet, bitter), dietary habits and BMI. We will also investigate the tooth microbiome in relation to dental caries and above mentioned factors and establish a model for large scale collection of oral microbiota.Dental caries is highly prevalent in Sweden and worldwide. The disease confers widespread suffering and an economic burden to the individual and society. In Sweden alone, the estimated annual cost for dental treatment exceeds 12 billion SEK of which 6 billions are state aid. For decades a decreasing disease trend has been seen in industrialized countries but this seems to revert, paralleled by increases in developing countries with social improvement. In Sweden, 10-15% represent a highly caries active group with constant treatment need, and in adults, most treatments are replacements due to recurrent caries from insufficient disease prevention. This illustrates that despite the massive impact of caries on global welfare, the underlying mechanisms of action and effective prevention and treatment paradigms are insufficient in susceptible individuals.We have established the international GLIDE consortium (Gene-Lifestyle Interactions and Dental End-points) including 11 Swedish and 7 international cohorts. Totally, approximately 130,000 subjects with information on caries, diet and cardiometabolic traits and more than 60% have genetic information (GWAS, MetaboChip, Tac-man); 88% are from population-based studies and others from twin or controls in case-control studies. Genome-wide association studies (GWAS) have led to that a large number of genetic variants associated with complex diseases (obesity, diabetes, etc.) have been discovered. The two GWAS-studies for caries have suggested candidate genes but none was statistically robust and none could be replicated in an independent study group. This likely reflects the complex nature of the caries disease and large heterogeneity in the population which calls for large samples for statistical power. We have identified gene candidates for caries in one of the Swedish cohorts (GLACIER), which together with the large size of the GLIDE cohort, form the conditions for successful identification of robust caries associated gene variants. The methods that will be used in the project includes a hypothesis free association study (GWAS-caries) with replication of gene variants passing a critical alpha level, traditional epidemiological association analyses, ?Mendelian randomization? for evaluation of causality between BMI and caries using a genetic risk score based on the BMI associated genotypes FTO, MC4R and TMEM18 as instrument for BMI, and mapping of the TAS1R2 (rs35874116 and rs9701796), TAS2R38 (rs713598), and GLUT2 (rs5400) genes for association analyses with diet, BMI and caries. The oral mikrobiota in caries and conditions identified in preceding analyses is characterized with multiplex sequencing (Illumina or PacBio) of the bacterial 16S rRNA gene and taxonomy resolution from the HOMD 16S RDNA database for oral bacteria (www.homd.org).Identifying caries genes and their role in behavior and bacterial ecology in the mouth and increased knowledge of other caries determinates will help designing treatment models for groups representing different types of caries. The project has a clinical relevance for the individual as well as in an overarching public health perspective. The project is a continuation of the grant Dnr 2011-337
Principal InvestigatorJohansson, Ingegerd
Coordinating organisation
Umeå University
Funder
Period
2016-01-01 - 2019-12-31
National Category
Dentistry
Identifiers
DiVA, id: project:1428Project, id: 2015-02597_VR

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