Genomics of periodontal disease and tooth morbidity

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..

Biologically Defined or Biologically Informed Traits Are More Heritable Than Clinically Defined Ones: The Case of Oral and Dental Phenotypes

“…In the oral health domain, the genomics evidence base is growing but remains insufficient to inform care for the common, non-syndromic forms of periodontitis and dental caries (Divaris 2019b). This is in contrast with early and consistent observations that considerable variation in oral disease is attributable to heritable factors (Morelli et al 2019). The genetic basis of oral health has long been theorized but little evidence exists on specific genetic factors underlying common oral and dental disease traits.…”

“…The clinical information, a follow-up telephone survey, and the collected biospecimens from the dental component of ARIC has been used to generate several oral/dental phenotypes. For the purposes of this study we examined the following trait domains: number of remaining natural teeth at the baseline examination, incident tooth loss [>2 teeth over a 10-year period, assessed via a telephone survey; (Naorungroj et al 2017)]; dental caries [DMFS index; (Wang et al 2012) and tooth morbidity, DM T FS index (Morelli et al 2019;Shungin et al 2019)]; periodontitis [defined using the CDC/AAP chronic periodontitis definition (Page, Eke 2013); the 2017 world workshop classification (WW17; Papapanou et al 2018); extent probing depth and attachment loss scores (Carlos et al 1986); mean interproximal attachment loss (Sanders et al 2017)]; periodontal profile classes (PPC; Morelli et al 2017;Morelli et al 2018); subgingival pathogen colonization (Divaris et al 2012); gingival crevicular fluid (GCF) interleukin(IL)-1β expression (Offenbacher et al 2018); and periodontal complex traits (PCT) (Offenbacher et al 2016). The PPC classification (Morelli et al 2017) entails an empirically derived 7-category taxonomy that accounts for intra-oral patterns of tooth loss whereas the 6 PCTs (Offenbacher et al 2016) are essentially vectors of "biological variance" [i.e., subgingival colonization patterns and host inflammatory response (GCF IL-1β), combined with clinical parameters] in periodontitis.…”

“…For example, most reports of the heritability of periodontitis indicate that up to a third of the population variance of periodontitis is due to genetic factors, with more severe disease forms being more strongly genetically controlled (Nibali et al 2019). Despite this evident heritability, the number of consensus genes linked to periodontitis is less than a handful (Morelli et al 2019;.…”

Biologically informed stratification of periodontal disease holds the key to achieving precision oral health

“…Additionally, the deep phenotyping studies in well-characterized clinical samples provide hypotheses that can be tested in mechanistic studies. A comprehensive summary of all genomics findings to date for periodontal disease is offered in a recent review by our group 15 and others. [16][17][18] We caution that until external validation and mechanistic confirmation of any identified loci for periodontal disease is done, such genetic findings should not be considered actionable in clinical practice.…”

Identification of Novel Genome-Wide Associations for Oral Inflammatory Traits

“…Although the exact mechanisms for the pathogenesis of different kinds of oral in ammatory diseases still need to be elucidated, an important takeaway from these studies is that genetic factors that regulate immune and in ammatory conditions may play an important role in the occurrence and susceptibility of these diseases [9]. However, the loci contributing to common traits or diseases may be disorder-speci c or shared between disorders.…”