Genetic study suggests a causal link between dental caries and cardiovascular- metabolic factors

According to the 2016 Global Burden of Diseases, Injuries and Risk Factors Study, dental caries in permanent teeth and periodontitis were the leading and 11th most prevalent causes of disease worldwide in 2016. Another study in 2015 estimated the global cost of dental diseases to be more than 540 billion US dollars. Even after knowing that the genetic contribution to oral health outcomes and the heritability of dental caries and periodontitis happens to be as high as 50%, the nature of this contribution remains poorly characterised. We know that an increased understanding of genetic factors can improve our knowledge of the aetiology and clinical management of oral diseases, yet the role of genes in oral health remains understudied. One of the reasons for this is that the complex nature of tooth decay and periodontitis requires extensive studies to draw firm conclusions.

Genome-wide association studies (GWAS) have been in use to study the genetic basis of dental caries and periodontitis. GWAS for dental caries have investigated - overall caries experience, specific presentations of disease and the presence or absence of disease in paediatric populations. However, to date, few reliable genetic-association signals have been found. GWAS for periodontitis have investigated the presence or absence of disease, quantitative measures of periodontal status, severe presentations of disease, molecular and microbial intermediaries of disease and composite phenotypes such as GWAS for principal components which aim to capture multiple facets of periodontal health. Even these studies, to date, have not yielded consistent evidence of specific genetic contributions to periodontitis.

One should know the difference between the genotype and the phenotype. A genotype is a part of the genetic makeup of an individual. Genotype interacts with the environment and imparts a phenotype - a set of observable characteristics in an individual. Genome-wide analyses need good statistical power for the studies.  The logistical and economic challenges in obtaining detailed and refined phenotypes in large populations have made the recent studies focus on taking advantage of extremely large, population-based, cohorts with both genetic data and less-refined proxy phenotypes. The need to work on highly refined phenotypes may reduce the sample size and subsequently the statistical power of the study. Hence studies have started working on large cohorts, focusing on the presence of less well defined but informative phenotypes. This trade-off has enabled the researchers to find successful association signal discoveries for several complex traits, yielding important biological insights. In order to achieve further understanding of genetic contributions to caries and periodontitis, a shift in analysis scale—afforded by a similar approach to measurement—is required.

In the current study, the researchers have synthesised evidence from two sources; the Gene-Lifestyle Interactions in Dental Endpoints (GLIDE) consortium, which is a unique collection of epidemiological cohorts with detailed information on clinical endpoints of dental diseases; and the UK Biobank (UKB), which contains less-refined self-reported oral health data at a larger scale. The UKB data alone may not be enough to yield adequate biological meaning and relevance of the approximate measures, but when combined with the more detailed clinical information in GLIDE, this combination of complementary resources provides great information on the genetic association.

Researchers, in order to fulfil the large data requirement, took the data from nine international clinical studies with 62,000 participants and merged it with the data on self-reported dental health from the UK Biobank, involving 461,000 participants. Ingegerd Johansson, Senior Professor at the Institute of Odontology, the lead researcher at Umeå University, said, “The study makes it clear that teeth are part of the body. Among other things, we can see that there seems to be a causal link between risk factors for cardiovascular disease and tooth decay.”

Using this combination of resources, the researchers could identify 47 novel risk loci for dental caries. The study showed that the heritability of dental caries is partially shared with a range of complex traits. The genes linked to tooth decay included those that help form teeth and the jawbone, those with protective functions in saliva and those which affect the bacteria found on the teeth. The research also confirmed a previously known immune-related gene to be linked to periodontitis.

The researchers used a technique called Mendelian randomisation, to find a genetic link between oral health and cardiovascular- metabolic risk factors such as smoking, obesity, education and personality. Applied analysis using Mendelian randomisation suggested that dental caries has undesirable downstream effects on general health. Together, these findings improve our understanding of the potential causes and consequences of an important complex disease. The researchers have stated that there might be a causal link between decay and some cardiovascular-metabolic risk factors.

The study, titled “Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data”, was published on 24 June in Nature Communications.

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