Abstract
In this review we critically summarize the evidence base and the progress to date regarding the genomic basis of periodontal disease and tooth morbidity (ie, dental caries and tooth loss), and discuss future applications and research directions in the context of precision oral health and care. Evidence for these oral/dental traits from genome‐wide association studies first emerged less than a decade ago. Basic and translational research activities in this domain are now under way by multiple groups around the world. Key departure points in the oral health genomics discourse are: (a) some heritable variation exists for periodontal and dental diseases; (b) the environmental component (eg, social determinants of health and behavioral risk factors) has a major influence on the population distribution but probably interacts with factors of innate susceptibility at the person‐level; (c) sizeable, multi‐ethnic, well‐characterized samples or cohorts with high‐quality measures on oral health outcomes and genomics information are required to make decisive discoveries; (d) challenges remain in the measurement of oral health and disease, with current periodontitis and dental caries traits capturing only a part of the health‐disease continuum, and are little or not informed by the underlying biology; (e) the substantial individual heterogeneity that exists in the clinical presentation and lifetime trajectory of oral disease can be identified and leveraged in a precision medicine framework or, if unappreciated, can hamper translational efforts. In this review we discuss how composite or biologically informed traits may offer improvements over clinically defined ones for the genomic interrogation of oral diseases. We demonstrate the utility of the results of genome‐wide association studies for the development and testing of a genetic risk score for severe periodontitis. We conclude that exciting opportunities lie ahead for improvements in the oral health of individual patients and populations via advances in our understanding of the genomic basis of oral health and disease. The pace of new discoveries and their equitable translation to practice will largely depend on investments in the education and training of the oral health care workforce, basic and population research, and sustained collaborative efforts..
Highlights
The existence of innate susceptibility and heritability of oral health and disease traits is well‐established
A recent, large‐scale, consor‐ tium meta‐analysis identified many loci associated with dental caries, providing a rich resource of candi‐ dates to be followed‐up in subsequent investigations
In a recent comprehensive genome‐ wide association study and mechanistic follow‐up investigation, our group recently reported that variants in the IL37 locus strongly controlled gingival crevicular fluid interleu‐ kin‐1beta expression (P = 3.3 × 10−22) and were associated with 10‐year incident tooth loss and aggressive periodontitis assessed in an independent cohort
Summary
The existence of innate susceptibility and heritability of oral health and disease traits is well‐established. As is the case with periodontitis, there are substantial variations and methodologic areas for improvement in the reported genome‐ wide association studies of dental caries, especially with clinical phe‐ notype ascertainment One such example pertains to the childhood disease domain, where primary teeth begin to shed after the age of 6 years, leading to the loss of potentially disease‐informative surfaces between the ages of 6 and 12 years (which is considered the age range of primary dentition caries). Case definitions and diagnostic criteria for both periodontitis and dental caries have evolved over time, mostly as a result of changes in their population prevalence and, to some degree, improvements in our understanding of the disease process.[75,76,77,78] For example, most genome‐wide association study evidence for periodontitis has been generated by studies that used clinical measures of prob‐ ing depth and attachment loss, whereas varying thresholds and criteria have been applied to derive person‐level dental caries experience indices.
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