James Beck - Academia.edu (original) (raw)
Papers by James Beck
Carolina Digital Repository (University of North Carolina at Chapel Hill), 2015
Background-Chronic kidney disease (CKD) remains a prevalent public health problem that disproport... more Background-Chronic kidney disease (CKD) remains a prevalent public health problem that disproportionately affects African Americans, despite intense efforts targeting traditional risk factors. Periodontal disease, a chronic bacterial infection of the oral cavity, is both common and modifiable and has been implicated as a novel potential CKD risk factor. We sought to examine to what extent periodontal disease is associated with kidney function decline. Methods-Retrospective cohort study of 699 African American participants with preserved kidney function defined by an estimated glomerular filtration rate (eGFR) >60ml/min/1.73m 2 at
Journal of Dental Research, Oct 1, 2016
Chronic periodontitis (CP) has a genetic component, particularly its severe forms. Evidence from ... more Chronic periodontitis (CP) has a genetic component, particularly its severe forms. Evidence from genome-wide association studies (GWASs) has highlighted several potential novel loci. Here, the authors report the first GWAS of CP among a large communitybased sample of Hispanics/Latinos. The authors interrogated a quantitative trait of CP (mean interproximal clinical attachment level determined by full-mouth periodontal examinations) among 10,935 adult participants (mean age: 45 y, range: 18 to 76 y) from the Hispanic Community Health Study / Study of Latinos. Genotyping was done with a custom Illumina Omni2.5M array, and imputation to approximately 20 million single-nucleotide polymorphisms was based on the 1000 Genomes Project phase 1 reference panel. Analyses were based on linear mixed models adjusting for sex, age, study design features, ancestry, and kinship and employed a conventional P < 5 × 10-8 statistical significance threshold. The authors identified a genome-wide significant association signal in the 1q42.2 locus (TSNAX-DISC1 noncoding RNA, lead single-nucleotide polymorphism: rs149133391, minor allele [C] frequency = 0.01, P = 7.9 × 10-9) and 4 more loci with suggestive evidence of association (P < 5 × 10-6): 1q22 (rs13373934), 5p15.33 (rs186066047), 6p22.3 (rs10456847), and 11p15.1 (rs75715012). We tested these loci for replication in independent samples of European-American (n = 4,402) and African-American (n = 908) participants of the Atherosclerosis Risk in Communities study. There was no replication among the European Americans; however, the TSNAX-DISC1 locus replicated in the African-American sample (rs149133391, minor allele frequency = 0.02, P = 9.1 × 10-3), while the 1q22 locus was directionally concordant and nominally significant (rs13373934, P = 4.0 × 10-2). This discovery GWAS of interproximal clinical attachment level-a measure of lifetime periodontal tissue destruction-was conducted in a large, community-based sample of Hispanic/Latinos. It identified a genome-wide significant locus that was independently replicated in an African-American population. Identifying this genetic marker offers direction for interrogation in subsequent genomic and experimental studies of CP.
Carolina Digital Repository (University of North Carolina at Chapel Hill), 2013
Objectives-This study charted the trajectories of dental caries, including decayed teeth, missing... more Objectives-This study charted the trajectories of dental caries, including decayed teeth, missing teeth, and filled teeth among older Americans over a 5-year period. In particular, it focused on racial differences in the levels of and rates of change in dental caries experience. Methods-Data came from the Piedmont Dental Study. The sample included 810 older Americans who were dentate at the baseline with up to 4 repeated observations between 1988 and 1994. Hierarchical linear models were employed in depicting intrapersonal and interpersonal differences in dental caries experience. Results-Different measures of caries outcomes exhibited distinct trajectories. On average, the number of decayed teeth decreased over time, whereas missing teeth increased. In contrast, the number of filled teeth remained stable during a 5-year period. Relative to their white counterparts, older black Americans had more decayed teeth and missing teeth but fewer filled teeth. Blacks and whites differed in the levels of dental caries but not in their rates of change except for missing teeth. Even when demographic and socioeconomic attributes were adjusted, racial variations in dental caries experience remained significant. Conclusions-Though significantly correlated, various dental caries outcomes move along different paths over time. In view of the persistent racial disparities in dental caries trajectories, future interventions to minimize such variations among older Americans in the levels of and the rates of change in dental caries experience are clearly warranted. * This research was supported by grants R21 DE19518 and R01 DE08060 (Bei Wu, PI) from the National Institute of Dental and Craniofacial Research. We thank Corey Remle, Lina Bai, and Lilly Y. Lee for their assistance in undertaking this research.
Carolina Digital Repository (University of North Carolina at Chapel Hill), 2007
Background-Smoking is recognized as the primary behavioural risk factor for periodontal attachmen... more Background-Smoking is recognized as the primary behavioural risk factor for periodontal attachment loss (AL), but confirmatory data from prospective cohort studies are scarce. Aim-To quantify the association between cigarette smoking patterns and AL by age 32. Methods-Periodontal examinations were conducted at ages 26 and 32 in a longstanding prospective study of a birth cohort born in Dunedin (New Zealand) in 1972/1973. Longitudinal categorization of smoking exposure was undertaken using data collected at ages 15, 18, 21, 26 and 32. Results-Complete data were available for 810 individuals of whom 48.9% had ever smoked (31.5% were current smokers). Compared with never-smokers, long-term smokers (and other age-32 smokers) had very high odds ratios (ORs of 7.1 and 5.7, respectively) for having 1 +sites with 5 +mm AL, and were more likely to be incident cases after age 26 (ORs of 5.2 and 3.2, respectively). Twothirds of new cases after age 26 were attributable to smoking. There were no significant differences in periodontal health between never-smokers and those who had quit smoking after age 26. Conclusions-Current and long-term smoking in young adults is detrimental to periodontal health, but smoking cessation may be associated with a relatively rapid improvement in the periodontium.
Journal of Dental Research, Aug 24, 2022
Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial disea... more Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and "precision," data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface-level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.
BMJ Open, 2012
Objectives: We examined the potential association between prior chronic obstructive pulmonary dis... more Objectives: We examined the potential association between prior chronic obstructive pulmonary disease (COPD) and edentulism, and whether the association varied by COPD severity using data from the Dental Atherosclerosis Risk in Communities Study.
medRxiv (Cold Spring Harbor Laboratory), Feb 10, 2023
doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by pee... more doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
Journal of Dental Research
Precise classification of periodontal disease has been the objective of concerted efforts and has... more Precise classification of periodontal disease has been the objective of concerted efforts and has led to the introduction of new consensus-based and data-driven classifications. The purpose of this study was to characterize the microbiological signatures of a latent class analysis (LCA)–derived periodontal stratification system, the Periodontal Profile Class (PPC) taxonomy. We used demographic, microbial (subgingival biofilm composition), and immunological data (serum IgG antibody levels, obtained with checkerboard immunoblotting technique) for 1,450 adult participants of the Dental Atherosclerosis Risk in Communities (ARIC) study, with already generated PPC classifications. Analyses relied on t tests and generalized linear models with Bonferroni correction. Men and African Americans had higher systemic antibody levels against most microorganisms compared to women and Caucasians ( P < 0.05). Healthy individuals (PPC-I) had low levels of biofilm bacteria and serum IgG levels again...
The Journal of Clinical Endocrinology & Metabolism, 2021
Purpose To determine whether periodontal disease is positively associated with incident diabetes ... more Purpose To determine whether periodontal disease is positively associated with incident diabetes across the continuum of body mass levels (BMI) and test the hypothesis that the periodontal risk for incident diabetes is modified by BMI. Methods We included 5569 diabetes-free participants from Visit 4 (1996-1998) of the Atherosclerosis Risk in Communities study and followed them until 2018. Periodontal disease status was classified by periodontal profile class (PPC)-Stages , and incident diabetes was based on participant report of physician diagnosis. We estimated the hazard ratios (HR) for diabetes using a competing risk model for each PPC-Stage. We assessed multiplicative interactions between periodontal disease and BMI (as a continuous variable) on risk of diabetes. Results During a median time of 19.4 years of follow-up, 1348 incident diabetes cases and 1529 deaths occurred. Compared to the “Health/Incidental Disease” stage, participants with PPC “Severe Periodontal Disease” or “S...
Nature communications, Sep 11, 2018
There is no agnostic GWAS evidence for the genetic control of IL-1β expression in periodontal dis... more There is no agnostic GWAS evidence for the genetic control of IL-1β expression in periodontal disease. Here we report a GWAS for "high" gingival crevicular fluid IL-1β expression among 4910 European-American adults and identify association signals in the IL37 locus. rs3811046 at this locus (p = 3.3 × 10) is associated with severe chronic periodontitis (OR = 1.50; 95% CI = 1.12-2.00), 10-year incident tooth loss (≥3 teeth: RR = 1.33; 95% CI = 1.09-1.62) and aggressive periodontitis (OR = 1.12; 95% CI = 1.01-1.26) in an independent sample of 4927 German/Dutch adults. The minor allele at rs3811046 is associated with increased expression of IL-1β in periodontal tissue. In RAW macrophages, PBMCs and transgenic mice, the IL37 variant increases expression of IL-1β and IL-6, inducing more severe periodontal disease, while IL-37 protein production is impaired and shows reduced cleavage by caspase-1. A second variant in the IL37 locus (rs2708943, p = 4.2 × 10) associates with attenu...
Human molecular genetics, May 8, 2016
Genome-wide association studies (GWAS) of chronic periodontitis (CP) defined by clinical criteria... more Genome-wide association studies (GWAS) of chronic periodontitis (CP) defined by clinical criteria alone have had modest success to-date. Here, we refine the CP phenotype by supplementing clinical data with biological intermediates of microbial burden (levels of 8 periodontal pathogens) and local inflammatory response [gingival crevicular fluid (GCF) IL-1β] and derive periodontal complex traits (PCTs) via principal component analysis. PCTs were carried forward to GWAS (∼2.5 million markers) to identify PCT-associated loci among 975 European-American adult participants of the Dental ARIC study. We sought to validate these findings for CP in the larger ARIC cohort (n=821 participants with severe CP, 2031-moderate CP, 1914-healthy/mild disease) and an independent German sample including 717 aggressive periodontitis cases and 4210 controls. We identified 6 PCTs with distinct microbial community/IL-1β structures, albeit with overlapping clinical presentations. PCT1 was characterized by a ...
Journal (Canadian Dental Association), 2002
Recent studies in periodontal medicine suggest a mild to moderate association between human perio... more Recent studies in periodontal medicine suggest a mild to moderate association between human periodontal disease and certain systemic disorders such as diabetes mellitus, pneumonia, heart disease and preterm birth. The latest evidence, presented at a symposium entitled Periodontal Health and Systemic Disorders, sponsored by the University of Western Ontario School of Dentistry, showed that indeed such an association is likely. New data suggest that this association is not indicated by traditional clinical signs of periodontal disease but rather by a cluster of host immune and inflammatory mediators. The coming era of periodontal medicine based upon molecular criteria will affect the future of periodontal diagnosis, treatment and professional practice.
PLoS ONE, 2013
Background: In COPD patients, fatal and non-fatal respiratory-related events are influenced by ag... more Background: In COPD patients, fatal and non-fatal respiratory-related events are influenced by age, severity of respiratory disease, and comorbidities. Objectives: Analyze the effects of edentulism, periodontal disease and systemic biomarkers of inflammation on the occurrence of serious fatal and non-fatal respiratory-related events among subjects with COPD. Methods: Cases were identified from Dental Atherosclerosis Risk in Communities study. Edentulism was defined as study participants without any natural teeth or implants. Participants with one or more natural teeth (comprising 11,378 subjects) were studied as dentate subjects. Periodontal disease status among dentate individuals was determined using the consensus definitions published by the joint Center for Disease Control/American Association of Periodontology working group). Adjusted Hazard Models are developed to evaluate the relationship between edentulism/periodontal disease and COPD Related Events. Models were then stratified by GOLD Stage I, II and III/IV. Serum biomarkers were also evaluated to explore the effect of systemic inflammation. Results: A statistically significant association was found between oral health status and COPD-related events, even adjusting for conditions such as hypertension, smoking and diabetes. Edentulous individuals who had been diagnosed with COPD had a higher incidence and were at greater risk of having a COPD related event (hospitalization and death) than individuals who had teeth and whose mouths had healthy periodontal status. However, being edentulous did not convey excess risk for COPD-related events for those study participants who were classified as GOLD III/IV at baseline. Finally, we showed that individuals who had levels of serum IL-6 in the highest two quartiles were at even higher risk for COPD-related events. Conclusions: These findings suggest that the risk for COPD-related events after adjusting for potential confounders may be attributable to both edentulism and elevated serum IL-6 levels.
Kidney International, 2009
Journal of Stroke and Cerebrovascular Diseases, 2013
Periodontal disease has been shown to be associated with incident stroke. We investigated whether... more Periodontal disease has been shown to be associated with incident stroke. We investigated whether periodontal disease is independently associated with recurrent vascular events and certain inflammatory markers in stroke/TIA patients. In this prospective longitudinal hospital-based cohort study, periodontal disease was assessed in stroke/TIA patients. High periodontal disease was defined as the highest tertile of extent (% of sites) with attachment loss ≥ 5 mm. Serum interleukin-6, high sensitivity C-reactive protein and soluble intracellular adhesion molecule-1 were measured. The patients were followed for recurrent vascular events-stroke, TIA, myocardial infarction and vascular death. In the 106 patients that were evaluated, 40 (38%) showed high periodontal disease and 27 (26%) had recurrent vascular events over a median of 24 months (range 12-24 months). High periodontal disease patients had higher levels of interleukin-6 (p=0.01) and soluble intracellular adhesion molecule-1 (p=0.03). High periodontal disease was associated with recurrent vascular events before (Log rank p=0.01, hazard ratio 2.6, 95% CI, 1.2-5.7) and after adjustment for significant confounders-age and stroke status (Hazard Ratio 2.5, 95% confidence interval, 1.1 to 5.5, p=0.03); adjustment for possible confounders age, males, years of education and cardioembolic strokes (hazard ratio 2.8, 95% confidence interval, 1.2-6.5, p=0.02); and adjustment for propensity score that accounted for all potential measured confounders (hazard ratio 2.8, 95% confidence interval,1.2-6.5, p=0.02). There is an independent association between high periodontal disease and recurrent vascular events in stroke/TIA patients. High periodontal disease is also associated with higher serum levels of interleukin-6 and soluble intracellular adhesion molecule-1.
Journal of Periodontology, 1996
We explored the association between social factors and adult periodontitis by comparing self‐repo... more We explored the association between social factors and adult periodontitis by comparing self‐reported information for daily strains and symptoms of depression in 71 cases and 77 controls. Cases and controls were selected from among 1,426 participants in the Erie County Risk Factor Study. We found differences among those who scored higher than their peers on measures of social strain. The odds ratio (OR) and 95% confidence interval (95% CI) for the association between case status and Role Strain score of 2.27 or more was 2.84, 95% CI = 1.08 to 7.46. We also examined serum antibody, dichotomized at the median, for three periodontal pathogens (Bacteroides forsythus [IgG Bf], Porphyromonas gingivalis [IgG Pg], Actinobacillus actinomycetemcomitans [IgG Aa]), and assessed interaction between antibody levels and a Depression score derived from the Brief Symptom Inventory. IgG Pg and IgG Aa were both strongly associated with case status (OR = 4.52, 95% CI = 1.99 to 10.3 and OR = 5.29, 95% C...
Journal of Periodontology, 1996
It is our central hypothesis that periodontal diseases, which are chronic Gramnegative infections... more It is our central hypothesis that periodontal diseases, which are chronic Gramnegative infections, represent a previously unrecognized risk factor for atherosclerosis and thromboembolic events. Previous studies have demonstrated an association between periodontal disease severity and risk of coronary heart disease and stroke. We hypothesize that this association may be due to an underlying inflammatory response trait, which places an individual at high risk for developing both periodontal disease and atherosclerosis. We further suggest that periodontal disease, once established, provides a biological burden of endotoxin (lipopolysaccharide) and inflammatory cytokines (especially TxA2, IL‐1β, PGE2, and TNF‐α) which serve to initiate and exacerbate atherogenesis' and thromboembolic events. A cohort study was conducted using combined data from the Normative Aging Study and the Dental Longitudinal Study sponsored by the United States Department of Veterans Affairs. Mean bone loss sc...
Journal of Oral and Maxillofacial Surgery, 2007
Purpose: Analyze in pregnant subjects the relationship between third molar periodontal pathology,... more Purpose: Analyze in pregnant subjects the relationship between third molar periodontal pathology, and subjects' overall periodontal status. Assess also, the associations between postpartum periodontal status by jaw and a systemic impact, preterm birth, or elevated serum C-reactive protein (CRP). Patients and Methods: Data were from an IRB-approved study, Oral Conditions and Pregnancy. In this clinical study, full-mouth periodontal examinations including third molars were conducted at greater than 24 weeks of pregnancy and again within 72 hours of delivery. For our analyses, mean periodontal probing depth (PD) by visible tooth and by jaw were calculated at enrollment and postpartum. Subjects were categorized by 3 broad levels of periodontal health, considered the primary outcome variable. The primary predictor variable for levels of periodontal health was the presence or absence of visible third molars. Mean periodontal probing depth in the mandible or maxilla at term was considered an indicator of a possible risk of systemic exposure, increasing the odds of preterm birth, less than 37 weeks gestation, or elevated serum CRP levels. Chi-square and t tests were used to determine statistical significance, .05. Significant predictor variables were included in multivariable models. Unconditional logistic multivariate models were used to derive odds ratios (OR) and 95% confidence intervals (CI). Results: Data from examinations at enrollment and postpartum were available for 1,020 and 891 subjects, respectively. Visible third molars were detected in 405 subjects at enrollment and in 360 subjects at term. No subjects had third molars removed during the study. At enrollment and postpartum, subjects with visible third molars were significantly more likely to have moderate/severe periodontal disease, 23.5% versus 8.5%, and 18.3 versus 9.4%, respectively. Mean PD was significantly greater for maxillary and mandibular molars than for more anterior teeth, P Ͻ .01. In both jaws, mean PD tended to be progressively greater from first to third molars. No differences were found in mean PD by jaw. In subjects with visible third molars, adjusting for the severity of mandibular periodontal disease, the level of maxillary periodontal disease was significantly associated with preterm birth, P Ͻ .01, OR 2.6 (95% CI 1.1-6.8), or the upper quartile of serum CRP at term, at least 23.0 mg/L postpartum, P ϭ .05, OR 2.5 (95% CI 1.2-5.1). Conclusions: Subjects' detected levels of periodontal disease were greater at enrollment and postpartum if visible third molars were detected.
Journal of Oral and Maxillofacial Surgery, 2006
This study examined the reliability of assessing clinical periodontal measures on third molars, a... more This study examined the reliability of assessing clinical periodontal measures on third molars, and the association between oral inflammation with periodontal pathology including third molars, and systemic inflammation including negative obstetric outcomes. Patients and Methods: Reliability of third molar probing depth (PD) was assessed for 41 patients by trained examiners. The data for the association between oral inflammation with periodontal pathology and systemic outcomes were derived from an IRB-approved study, "Oral Conditions and Pregnancy." Full mouth periodontal exams including third molars were conducted at less than 24 weeks of pregnancy. Periodontal status, moderate/severe periodontal disease (15 or more sites PD Ն4 mm) was considered as a possible predictor of systemic inflammation and pre-term birth. The upper quartile of the extent of PD for third molars alone (PD Ն4 mm) also was considered as a possible exposure variable for the same outcomes. Chi-square and t tests were used to determine statistical significance (0.05). Significant predictor variables were included in multivariate models. Unconditional logistic multivariate models were used to derive odds ratios (OR) and 95% confidence intervals (CI). Results: Reliability of PD within 1 mm was excellent, and similar for third molars and non-third molars. Data from 1,020 obstetric patients were available for analysis. Eighteen percent of the patients delivered preterm, at less than 37 weeks. Having moderate/severe periodontal disease excluding third molars, was significantly associated with preterm birth (P ϭ .008). Results were more significant if third molars were included (P ϭ .0005). With multivariate models moderate/severe periodontal disease at enrollment including third molar PD, was associated with preterm birth (OR, 1.7; 95% CI, 1.1, 2.6). If only the extent of third molar PD was considered, odds also were increased for preterm birth (OR, 2.4; 95% CI, 1.1, 5.2). If only the extent of third molar PD was considered at enrollment, odds were increased for serum markers of systemic inflammation, elevated serum CRP, and oxidative stress, 8-isoPGF 2␣. Conclusions: Dental examiners could reliably assess clinical periodontal measures on third molars. Third molars should be included in studies of systemic outcomes associated with oral inflammation. Women of child-bearing age should be made aware of the systemic risks of oral inflammation with third molar periodontal pathology.
Clinical Journal of the American Society of Nephrology, 2007
The relationship between periodontitis and two measures of systemic inflammation, serum albumin a... more The relationship between periodontitis and two measures of systemic inflammation, serum albumin and C-reactive protein (CRP), were examined among patients who were receiving chronic outpatient hemodialysis. Adult patients at two locations, North Carolina and New York City, were evaluated by dentist examiners. Six sites per tooth (up to 32 teeth per patient) were examined. A periodontitis case was defined as >60% of sites with attachment level >4 mm. Multivariable logistic regression was used to determine the association of periodontitis with low serum albumin, defined as <3.5 mg/dl, and with high CRP, defined as >3.0 mg/dl. A total of 154 patients completed the study. The mean age was 54.6 yr (SD 13.3), and average duration of dialysis was 4.0 yr (3 mo to 16 yr). Eighty-six (54.6%) were men, and 89 (58.2%) were black. Common causes of end-stage kidney disease were hypertension (12.3%), diabetes (22.1%), glomerulonephritis (7.1%), and other (58.4%). The average number of teeth was 20.3 (SD 8.4). Thirty-five (23%) patients were periodontitis cases. Severe periodontitis was associated with low serum albumin (odds ratio 8.20; 95% confidence interval 1.61 to 41.82; P ؍ 0.01) compared with individuals without severe periodontitis disease after adjustment for age, gender, race, diabetes, hypertension, body mass index, smoking, study site, total cholesterol, serum calcium, serum phosphorus, and normalized protein catabolic rate. There was no observed association of severe periodontitis with CRP. Investigation of the potential contribution of periodontitis to serum albumin and possibly to morbidity and mortality among patients with end-stage kidney disease seems warranted.
Carolina Digital Repository (University of North Carolina at Chapel Hill), 2015
Background-Chronic kidney disease (CKD) remains a prevalent public health problem that disproport... more Background-Chronic kidney disease (CKD) remains a prevalent public health problem that disproportionately affects African Americans, despite intense efforts targeting traditional risk factors. Periodontal disease, a chronic bacterial infection of the oral cavity, is both common and modifiable and has been implicated as a novel potential CKD risk factor. We sought to examine to what extent periodontal disease is associated with kidney function decline. Methods-Retrospective cohort study of 699 African American participants with preserved kidney function defined by an estimated glomerular filtration rate (eGFR) >60ml/min/1.73m 2 at
Journal of Dental Research, Oct 1, 2016
Chronic periodontitis (CP) has a genetic component, particularly its severe forms. Evidence from ... more Chronic periodontitis (CP) has a genetic component, particularly its severe forms. Evidence from genome-wide association studies (GWASs) has highlighted several potential novel loci. Here, the authors report the first GWAS of CP among a large communitybased sample of Hispanics/Latinos. The authors interrogated a quantitative trait of CP (mean interproximal clinical attachment level determined by full-mouth periodontal examinations) among 10,935 adult participants (mean age: 45 y, range: 18 to 76 y) from the Hispanic Community Health Study / Study of Latinos. Genotyping was done with a custom Illumina Omni2.5M array, and imputation to approximately 20 million single-nucleotide polymorphisms was based on the 1000 Genomes Project phase 1 reference panel. Analyses were based on linear mixed models adjusting for sex, age, study design features, ancestry, and kinship and employed a conventional P < 5 × 10-8 statistical significance threshold. The authors identified a genome-wide significant association signal in the 1q42.2 locus (TSNAX-DISC1 noncoding RNA, lead single-nucleotide polymorphism: rs149133391, minor allele [C] frequency = 0.01, P = 7.9 × 10-9) and 4 more loci with suggestive evidence of association (P < 5 × 10-6): 1q22 (rs13373934), 5p15.33 (rs186066047), 6p22.3 (rs10456847), and 11p15.1 (rs75715012). We tested these loci for replication in independent samples of European-American (n = 4,402) and African-American (n = 908) participants of the Atherosclerosis Risk in Communities study. There was no replication among the European Americans; however, the TSNAX-DISC1 locus replicated in the African-American sample (rs149133391, minor allele frequency = 0.02, P = 9.1 × 10-3), while the 1q22 locus was directionally concordant and nominally significant (rs13373934, P = 4.0 × 10-2). This discovery GWAS of interproximal clinical attachment level-a measure of lifetime periodontal tissue destruction-was conducted in a large, community-based sample of Hispanic/Latinos. It identified a genome-wide significant locus that was independently replicated in an African-American population. Identifying this genetic marker offers direction for interrogation in subsequent genomic and experimental studies of CP.
Carolina Digital Repository (University of North Carolina at Chapel Hill), 2013
Objectives-This study charted the trajectories of dental caries, including decayed teeth, missing... more Objectives-This study charted the trajectories of dental caries, including decayed teeth, missing teeth, and filled teeth among older Americans over a 5-year period. In particular, it focused on racial differences in the levels of and rates of change in dental caries experience. Methods-Data came from the Piedmont Dental Study. The sample included 810 older Americans who were dentate at the baseline with up to 4 repeated observations between 1988 and 1994. Hierarchical linear models were employed in depicting intrapersonal and interpersonal differences in dental caries experience. Results-Different measures of caries outcomes exhibited distinct trajectories. On average, the number of decayed teeth decreased over time, whereas missing teeth increased. In contrast, the number of filled teeth remained stable during a 5-year period. Relative to their white counterparts, older black Americans had more decayed teeth and missing teeth but fewer filled teeth. Blacks and whites differed in the levels of dental caries but not in their rates of change except for missing teeth. Even when demographic and socioeconomic attributes were adjusted, racial variations in dental caries experience remained significant. Conclusions-Though significantly correlated, various dental caries outcomes move along different paths over time. In view of the persistent racial disparities in dental caries trajectories, future interventions to minimize such variations among older Americans in the levels of and the rates of change in dental caries experience are clearly warranted. * This research was supported by grants R21 DE19518 and R01 DE08060 (Bei Wu, PI) from the National Institute of Dental and Craniofacial Research. We thank Corey Remle, Lina Bai, and Lilly Y. Lee for their assistance in undertaking this research.
Carolina Digital Repository (University of North Carolina at Chapel Hill), 2007
Background-Smoking is recognized as the primary behavioural risk factor for periodontal attachmen... more Background-Smoking is recognized as the primary behavioural risk factor for periodontal attachment loss (AL), but confirmatory data from prospective cohort studies are scarce. Aim-To quantify the association between cigarette smoking patterns and AL by age 32. Methods-Periodontal examinations were conducted at ages 26 and 32 in a longstanding prospective study of a birth cohort born in Dunedin (New Zealand) in 1972/1973. Longitudinal categorization of smoking exposure was undertaken using data collected at ages 15, 18, 21, 26 and 32. Results-Complete data were available for 810 individuals of whom 48.9% had ever smoked (31.5% were current smokers). Compared with never-smokers, long-term smokers (and other age-32 smokers) had very high odds ratios (ORs of 7.1 and 5.7, respectively) for having 1 +sites with 5 +mm AL, and were more likely to be incident cases after age 26 (ORs of 5.2 and 3.2, respectively). Twothirds of new cases after age 26 were attributable to smoking. There were no significant differences in periodontal health between never-smokers and those who had quit smoking after age 26. Conclusions-Current and long-term smoking in young adults is detrimental to periodontal health, but smoking cessation may be associated with a relatively rapid improvement in the periodontium.
Journal of Dental Research, Aug 24, 2022
Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial disea... more Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and "precision," data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface-level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.
BMJ Open, 2012
Objectives: We examined the potential association between prior chronic obstructive pulmonary dis... more Objectives: We examined the potential association between prior chronic obstructive pulmonary disease (COPD) and edentulism, and whether the association varied by COPD severity using data from the Dental Atherosclerosis Risk in Communities Study.
medRxiv (Cold Spring Harbor Laboratory), Feb 10, 2023
doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by pee... more doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
Journal of Dental Research
Precise classification of periodontal disease has been the objective of concerted efforts and has... more Precise classification of periodontal disease has been the objective of concerted efforts and has led to the introduction of new consensus-based and data-driven classifications. The purpose of this study was to characterize the microbiological signatures of a latent class analysis (LCA)–derived periodontal stratification system, the Periodontal Profile Class (PPC) taxonomy. We used demographic, microbial (subgingival biofilm composition), and immunological data (serum IgG antibody levels, obtained with checkerboard immunoblotting technique) for 1,450 adult participants of the Dental Atherosclerosis Risk in Communities (ARIC) study, with already generated PPC classifications. Analyses relied on t tests and generalized linear models with Bonferroni correction. Men and African Americans had higher systemic antibody levels against most microorganisms compared to women and Caucasians ( P < 0.05). Healthy individuals (PPC-I) had low levels of biofilm bacteria and serum IgG levels again...
The Journal of Clinical Endocrinology & Metabolism, 2021
Purpose To determine whether periodontal disease is positively associated with incident diabetes ... more Purpose To determine whether periodontal disease is positively associated with incident diabetes across the continuum of body mass levels (BMI) and test the hypothesis that the periodontal risk for incident diabetes is modified by BMI. Methods We included 5569 diabetes-free participants from Visit 4 (1996-1998) of the Atherosclerosis Risk in Communities study and followed them until 2018. Periodontal disease status was classified by periodontal profile class (PPC)-Stages , and incident diabetes was based on participant report of physician diagnosis. We estimated the hazard ratios (HR) for diabetes using a competing risk model for each PPC-Stage. We assessed multiplicative interactions between periodontal disease and BMI (as a continuous variable) on risk of diabetes. Results During a median time of 19.4 years of follow-up, 1348 incident diabetes cases and 1529 deaths occurred. Compared to the “Health/Incidental Disease” stage, participants with PPC “Severe Periodontal Disease” or “S...
Nature communications, Sep 11, 2018
There is no agnostic GWAS evidence for the genetic control of IL-1β expression in periodontal dis... more There is no agnostic GWAS evidence for the genetic control of IL-1β expression in periodontal disease. Here we report a GWAS for "high" gingival crevicular fluid IL-1β expression among 4910 European-American adults and identify association signals in the IL37 locus. rs3811046 at this locus (p = 3.3 × 10) is associated with severe chronic periodontitis (OR = 1.50; 95% CI = 1.12-2.00), 10-year incident tooth loss (≥3 teeth: RR = 1.33; 95% CI = 1.09-1.62) and aggressive periodontitis (OR = 1.12; 95% CI = 1.01-1.26) in an independent sample of 4927 German/Dutch adults. The minor allele at rs3811046 is associated with increased expression of IL-1β in periodontal tissue. In RAW macrophages, PBMCs and transgenic mice, the IL37 variant increases expression of IL-1β and IL-6, inducing more severe periodontal disease, while IL-37 protein production is impaired and shows reduced cleavage by caspase-1. A second variant in the IL37 locus (rs2708943, p = 4.2 × 10) associates with attenu...
Human molecular genetics, May 8, 2016
Genome-wide association studies (GWAS) of chronic periodontitis (CP) defined by clinical criteria... more Genome-wide association studies (GWAS) of chronic periodontitis (CP) defined by clinical criteria alone have had modest success to-date. Here, we refine the CP phenotype by supplementing clinical data with biological intermediates of microbial burden (levels of 8 periodontal pathogens) and local inflammatory response [gingival crevicular fluid (GCF) IL-1β] and derive periodontal complex traits (PCTs) via principal component analysis. PCTs were carried forward to GWAS (∼2.5 million markers) to identify PCT-associated loci among 975 European-American adult participants of the Dental ARIC study. We sought to validate these findings for CP in the larger ARIC cohort (n=821 participants with severe CP, 2031-moderate CP, 1914-healthy/mild disease) and an independent German sample including 717 aggressive periodontitis cases and 4210 controls. We identified 6 PCTs with distinct microbial community/IL-1β structures, albeit with overlapping clinical presentations. PCT1 was characterized by a ...
Journal (Canadian Dental Association), 2002
Recent studies in periodontal medicine suggest a mild to moderate association between human perio... more Recent studies in periodontal medicine suggest a mild to moderate association between human periodontal disease and certain systemic disorders such as diabetes mellitus, pneumonia, heart disease and preterm birth. The latest evidence, presented at a symposium entitled Periodontal Health and Systemic Disorders, sponsored by the University of Western Ontario School of Dentistry, showed that indeed such an association is likely. New data suggest that this association is not indicated by traditional clinical signs of periodontal disease but rather by a cluster of host immune and inflammatory mediators. The coming era of periodontal medicine based upon molecular criteria will affect the future of periodontal diagnosis, treatment and professional practice.
PLoS ONE, 2013
Background: In COPD patients, fatal and non-fatal respiratory-related events are influenced by ag... more Background: In COPD patients, fatal and non-fatal respiratory-related events are influenced by age, severity of respiratory disease, and comorbidities. Objectives: Analyze the effects of edentulism, periodontal disease and systemic biomarkers of inflammation on the occurrence of serious fatal and non-fatal respiratory-related events among subjects with COPD. Methods: Cases were identified from Dental Atherosclerosis Risk in Communities study. Edentulism was defined as study participants without any natural teeth or implants. Participants with one or more natural teeth (comprising 11,378 subjects) were studied as dentate subjects. Periodontal disease status among dentate individuals was determined using the consensus definitions published by the joint Center for Disease Control/American Association of Periodontology working group). Adjusted Hazard Models are developed to evaluate the relationship between edentulism/periodontal disease and COPD Related Events. Models were then stratified by GOLD Stage I, II and III/IV. Serum biomarkers were also evaluated to explore the effect of systemic inflammation. Results: A statistically significant association was found between oral health status and COPD-related events, even adjusting for conditions such as hypertension, smoking and diabetes. Edentulous individuals who had been diagnosed with COPD had a higher incidence and were at greater risk of having a COPD related event (hospitalization and death) than individuals who had teeth and whose mouths had healthy periodontal status. However, being edentulous did not convey excess risk for COPD-related events for those study participants who were classified as GOLD III/IV at baseline. Finally, we showed that individuals who had levels of serum IL-6 in the highest two quartiles were at even higher risk for COPD-related events. Conclusions: These findings suggest that the risk for COPD-related events after adjusting for potential confounders may be attributable to both edentulism and elevated serum IL-6 levels.
Kidney International, 2009
Journal of Stroke and Cerebrovascular Diseases, 2013
Periodontal disease has been shown to be associated with incident stroke. We investigated whether... more Periodontal disease has been shown to be associated with incident stroke. We investigated whether periodontal disease is independently associated with recurrent vascular events and certain inflammatory markers in stroke/TIA patients. In this prospective longitudinal hospital-based cohort study, periodontal disease was assessed in stroke/TIA patients. High periodontal disease was defined as the highest tertile of extent (% of sites) with attachment loss ≥ 5 mm. Serum interleukin-6, high sensitivity C-reactive protein and soluble intracellular adhesion molecule-1 were measured. The patients were followed for recurrent vascular events-stroke, TIA, myocardial infarction and vascular death. In the 106 patients that were evaluated, 40 (38%) showed high periodontal disease and 27 (26%) had recurrent vascular events over a median of 24 months (range 12-24 months). High periodontal disease patients had higher levels of interleukin-6 (p=0.01) and soluble intracellular adhesion molecule-1 (p=0.03). High periodontal disease was associated with recurrent vascular events before (Log rank p=0.01, hazard ratio 2.6, 95% CI, 1.2-5.7) and after adjustment for significant confounders-age and stroke status (Hazard Ratio 2.5, 95% confidence interval, 1.1 to 5.5, p=0.03); adjustment for possible confounders age, males, years of education and cardioembolic strokes (hazard ratio 2.8, 95% confidence interval, 1.2-6.5, p=0.02); and adjustment for propensity score that accounted for all potential measured confounders (hazard ratio 2.8, 95% confidence interval,1.2-6.5, p=0.02). There is an independent association between high periodontal disease and recurrent vascular events in stroke/TIA patients. High periodontal disease is also associated with higher serum levels of interleukin-6 and soluble intracellular adhesion molecule-1.
Journal of Periodontology, 1996
We explored the association between social factors and adult periodontitis by comparing self‐repo... more We explored the association between social factors and adult periodontitis by comparing self‐reported information for daily strains and symptoms of depression in 71 cases and 77 controls. Cases and controls were selected from among 1,426 participants in the Erie County Risk Factor Study. We found differences among those who scored higher than their peers on measures of social strain. The odds ratio (OR) and 95% confidence interval (95% CI) for the association between case status and Role Strain score of 2.27 or more was 2.84, 95% CI = 1.08 to 7.46. We also examined serum antibody, dichotomized at the median, for three periodontal pathogens (Bacteroides forsythus [IgG Bf], Porphyromonas gingivalis [IgG Pg], Actinobacillus actinomycetemcomitans [IgG Aa]), and assessed interaction between antibody levels and a Depression score derived from the Brief Symptom Inventory. IgG Pg and IgG Aa were both strongly associated with case status (OR = 4.52, 95% CI = 1.99 to 10.3 and OR = 5.29, 95% C...
Journal of Periodontology, 1996
It is our central hypothesis that periodontal diseases, which are chronic Gramnegative infections... more It is our central hypothesis that periodontal diseases, which are chronic Gramnegative infections, represent a previously unrecognized risk factor for atherosclerosis and thromboembolic events. Previous studies have demonstrated an association between periodontal disease severity and risk of coronary heart disease and stroke. We hypothesize that this association may be due to an underlying inflammatory response trait, which places an individual at high risk for developing both periodontal disease and atherosclerosis. We further suggest that periodontal disease, once established, provides a biological burden of endotoxin (lipopolysaccharide) and inflammatory cytokines (especially TxA2, IL‐1β, PGE2, and TNF‐α) which serve to initiate and exacerbate atherogenesis' and thromboembolic events. A cohort study was conducted using combined data from the Normative Aging Study and the Dental Longitudinal Study sponsored by the United States Department of Veterans Affairs. Mean bone loss sc...
Journal of Oral and Maxillofacial Surgery, 2007
Purpose: Analyze in pregnant subjects the relationship between third molar periodontal pathology,... more Purpose: Analyze in pregnant subjects the relationship between third molar periodontal pathology, and subjects' overall periodontal status. Assess also, the associations between postpartum periodontal status by jaw and a systemic impact, preterm birth, or elevated serum C-reactive protein (CRP). Patients and Methods: Data were from an IRB-approved study, Oral Conditions and Pregnancy. In this clinical study, full-mouth periodontal examinations including third molars were conducted at greater than 24 weeks of pregnancy and again within 72 hours of delivery. For our analyses, mean periodontal probing depth (PD) by visible tooth and by jaw were calculated at enrollment and postpartum. Subjects were categorized by 3 broad levels of periodontal health, considered the primary outcome variable. The primary predictor variable for levels of periodontal health was the presence or absence of visible third molars. Mean periodontal probing depth in the mandible or maxilla at term was considered an indicator of a possible risk of systemic exposure, increasing the odds of preterm birth, less than 37 weeks gestation, or elevated serum CRP levels. Chi-square and t tests were used to determine statistical significance, .05. Significant predictor variables were included in multivariable models. Unconditional logistic multivariate models were used to derive odds ratios (OR) and 95% confidence intervals (CI). Results: Data from examinations at enrollment and postpartum were available for 1,020 and 891 subjects, respectively. Visible third molars were detected in 405 subjects at enrollment and in 360 subjects at term. No subjects had third molars removed during the study. At enrollment and postpartum, subjects with visible third molars were significantly more likely to have moderate/severe periodontal disease, 23.5% versus 8.5%, and 18.3 versus 9.4%, respectively. Mean PD was significantly greater for maxillary and mandibular molars than for more anterior teeth, P Ͻ .01. In both jaws, mean PD tended to be progressively greater from first to third molars. No differences were found in mean PD by jaw. In subjects with visible third molars, adjusting for the severity of mandibular periodontal disease, the level of maxillary periodontal disease was significantly associated with preterm birth, P Ͻ .01, OR 2.6 (95% CI 1.1-6.8), or the upper quartile of serum CRP at term, at least 23.0 mg/L postpartum, P ϭ .05, OR 2.5 (95% CI 1.2-5.1). Conclusions: Subjects' detected levels of periodontal disease were greater at enrollment and postpartum if visible third molars were detected.
Journal of Oral and Maxillofacial Surgery, 2006
This study examined the reliability of assessing clinical periodontal measures on third molars, a... more This study examined the reliability of assessing clinical periodontal measures on third molars, and the association between oral inflammation with periodontal pathology including third molars, and systemic inflammation including negative obstetric outcomes. Patients and Methods: Reliability of third molar probing depth (PD) was assessed for 41 patients by trained examiners. The data for the association between oral inflammation with periodontal pathology and systemic outcomes were derived from an IRB-approved study, "Oral Conditions and Pregnancy." Full mouth periodontal exams including third molars were conducted at less than 24 weeks of pregnancy. Periodontal status, moderate/severe periodontal disease (15 or more sites PD Ն4 mm) was considered as a possible predictor of systemic inflammation and pre-term birth. The upper quartile of the extent of PD for third molars alone (PD Ն4 mm) also was considered as a possible exposure variable for the same outcomes. Chi-square and t tests were used to determine statistical significance (0.05). Significant predictor variables were included in multivariate models. Unconditional logistic multivariate models were used to derive odds ratios (OR) and 95% confidence intervals (CI). Results: Reliability of PD within 1 mm was excellent, and similar for third molars and non-third molars. Data from 1,020 obstetric patients were available for analysis. Eighteen percent of the patients delivered preterm, at less than 37 weeks. Having moderate/severe periodontal disease excluding third molars, was significantly associated with preterm birth (P ϭ .008). Results were more significant if third molars were included (P ϭ .0005). With multivariate models moderate/severe periodontal disease at enrollment including third molar PD, was associated with preterm birth (OR, 1.7; 95% CI, 1.1, 2.6). If only the extent of third molar PD was considered, odds also were increased for preterm birth (OR, 2.4; 95% CI, 1.1, 5.2). If only the extent of third molar PD was considered at enrollment, odds were increased for serum markers of systemic inflammation, elevated serum CRP, and oxidative stress, 8-isoPGF 2␣. Conclusions: Dental examiners could reliably assess clinical periodontal measures on third molars. Third molars should be included in studies of systemic outcomes associated with oral inflammation. Women of child-bearing age should be made aware of the systemic risks of oral inflammation with third molar periodontal pathology.
Clinical Journal of the American Society of Nephrology, 2007
The relationship between periodontitis and two measures of systemic inflammation, serum albumin a... more The relationship between periodontitis and two measures of systemic inflammation, serum albumin and C-reactive protein (CRP), were examined among patients who were receiving chronic outpatient hemodialysis. Adult patients at two locations, North Carolina and New York City, were evaluated by dentist examiners. Six sites per tooth (up to 32 teeth per patient) were examined. A periodontitis case was defined as >60% of sites with attachment level >4 mm. Multivariable logistic regression was used to determine the association of periodontitis with low serum albumin, defined as <3.5 mg/dl, and with high CRP, defined as >3.0 mg/dl. A total of 154 patients completed the study. The mean age was 54.6 yr (SD 13.3), and average duration of dialysis was 4.0 yr (3 mo to 16 yr). Eighty-six (54.6%) were men, and 89 (58.2%) were black. Common causes of end-stage kidney disease were hypertension (12.3%), diabetes (22.1%), glomerulonephritis (7.1%), and other (58.4%). The average number of teeth was 20.3 (SD 8.4). Thirty-five (23%) patients were periodontitis cases. Severe periodontitis was associated with low serum albumin (odds ratio 8.20; 95% confidence interval 1.61 to 41.82; P ؍ 0.01) compared with individuals without severe periodontitis disease after adjustment for age, gender, race, diabetes, hypertension, body mass index, smoking, study site, total cholesterol, serum calcium, serum phosphorus, and normalized protein catabolic rate. There was no observed association of severe periodontitis with CRP. Investigation of the potential contribution of periodontitis to serum albumin and possibly to morbidity and mortality among patients with end-stage kidney disease seems warranted.