Chronic Periodontitis Research Articles

Exploring the plausible genetic relationship of salivary and tongue microbiome with periodontitis: A mendelian randomization study.

It is known that periodontitis is a multifactorial chronic irreversible inflammatory disease that affects the supporting structures of the teeth, initiated and spread by a complex interaction between periopathogens and the host's immune system. It begins with a microbial infection, followed by periodontal tissue damage caused by leukocyte hyperactivity, cytokines, eicosanoids and matrix metalloproteinases. Based on the assessment of their diagnostic properties, the most informative laboratory biomarkers of oral fluid microflora, proteolytic enzymes cathepsin, elastase, haptoglobin, IL-1, IL-4, IL-6, IL-8, IL-10 and TNF-α were determined in gingivitis and chronic periodontitis. It allows to evaluate the diagnostic efficiency of these markers in patients with periodontal diseases and to use them for early diagnosis in non-invasive diagnostics [1].

Hypercholesterolemia may exacerbate chronic periodontitis (CP) but the mechanism is uncertain. 27-Hydroxycholesterol (27HC) is metabolized from cholesterol through the action of cytochrome P450 27A1 (CYP27A1) and may participate in diseases associated with high cholesterol. This study aimed to examine the pro-inflammatory effects of 27HC, its role in hypercholesterolemia-aggravated CP, and the therapeutic action of felodipine, an inhibitor of CYP27A1. J774 murine macrophages were used. The levels of cholesterol, 27HC, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and CC chemokine ligand 2 (CCL2) were measured. Ligature-induced periodontitis was established in male rats fed with a normal diet (ND) or a high-fat/high-cholesterol diet (HFHCD). Disease progression was evaluated by micro-computed tomography, histology, and immunohistochemistry. Cholesterol enhanced the production of 27HC in macrophages, which promoted the expressions of iNOS, COX-2 and CCL2. HFHCD rats had hypercholesterolemia, higher serum and gingival 27HC, and more advanced periodontitis compared to ND rats. Felodipine suppressed cholesterol-induced 27HC production in macrophages. Felodipine treatment did not affect serum cholesterol but significantly decreased serum and gingival 27HC and alleviated ligature-induced periodontitis. Our data support the importance of 27HC in mediating hypercholesterolemia-aggravated periodontitis. Inhibiting 27HC production may have therapeutic value in periodontitis or other inflammatory diseases exacerbated by high cholesterol.

Dentofacial anomalies are closely linked to dental health, including caries and periodontal disease. This study examined the potential causal relationship between genetic variations associated with dental anomalies, such as malocclusion, and the risk of dental caries. A two-sample Mendelian randomization (MR) using genome-wide association studies (GWAS) data was conducted. Dental caries data were obtained from the UKB and GWAS catalog, while dental anomaly data came from FinnGen R12. The primary analysis used inverse-variance weighted (IVW) methods, with weighted median, MR-Egger, and weighted models for validation. Horizontal pleiotropy and outliers were assessed via MR-Egger and MR-PRESSO, while Cochran's Q test evaluated heterogeneity. Leave-One-Out (LOO) analysis identified predominant instrumental variables (IVs). The genetic prediction results indicated no statistically significant causal associations between dentofacial anomalies and dental caries (for all three cohorts, p>0.05). Also, IVW indicated no causal associations between dentofacial anomalies and other health problems, including mouth ulcers, toothache, loose teeth, bleeding gums, acute and chronic periodontitis, and painful gums. However, for the outcome of loose teeth, analysis revealed evidence of heterogeneity and suggested potential horizontal pleiotropy, with rs79490532 identified as a outlier. After removing rs79490532, the estimated causal effect of dentofacial anomalies on loose teeth remained statistically non-significant. Our findings suggest that dentofacial anomalies, including malocclusion, do not have a direct genetic impact on dental health. These results emphasize the importance of prioritizing oral hygiene practices, dietary interventions, and targeted preventive strategies over corrective orthodontic approaches in clinical management to improve dental health outcomes.

Objective: This systematic review aimed to determine how mediators establish a causal association between chronic periodontitis and adverse pregnancy outcomes (APOs). Methodology: The PRISMA 2020 guidelines were followed. Studies were selected using the PECO model to assess the inflammatory mediators linking chronic periodontitis and APOs. Six databases (PubMed, Scopus, Web of Science, Embase, Cochrane Library (CENTRAL) and Google Scholar) were searched from May 15-20, 2025. Inclusion criteria targeted English-language studies (2000-2025) reporting inflammatory markers in periodontitis-affected pregnancies. Case reports, editorials, conference abstracts, grey literature, in vitro studies and studies involving subjects other than humans, rats and baboons were excluded. Two independent reviewers screened and extracted data. The risk of bias was assessed using ROBINS-I, NOS or ROBIS tools. A qualitative synthesis of findings was performed. Results: Periodontitis is strongly linked to APOs, including gestational diabetes mellitus (GDM), preterm deliveries, preeclampsia and low birth weight (LBW). Inflammatory mediators, such as TNF-α, IL-1β, IL-6, IL-8, CRP, PGE2, MCP-1 and MMPs, are elevated, disrupting placental function. Conclusion: Periodontitis is strongly associated with APOs through direct microbial invasion and indirectly through systemic inflammatory mediators, which disrupt placental function and the fetus’s development. These findings highlight that a healthy periodontium is crucial in preventing complications like GDM, preeclampsia, preterm deliveries and LBW.

Sulfiredoxin levels in gingival crevicular fluid: A new antioxidant defence system- case control study.

ABSTRACTTo investigate the potential bidirectional causal relationship between specific blood metabolites and chronic periodontitis using Mendelian randomisation (MR). A two‐sample bidirectional MR analysis was conducted. Data on 1400 blood metabolites were obtained from a genome‐wide association study involving 8299 participants. Chronic periodontitis data were sourced from the FinnGen consortium, comprising 4784 cases and 272,252 controls. The primary analysis involved the inverse‐variance weighted (IVW) method. Furthermore, a metabolic pathway enrichment analysis was conducted on the metabolites identified by the IVW method. Following IVW and sensitivity analyses, 60 blood metabolites were found to be associated with chronic periodontitis. Metabolic pathway analysis suggested that these metabolites may influence chronic periodontitis through four pathways: pyrimidine metabolism, glycine, serine and threonine metabolism, arginine and proline metabolism and riboflavin metabolism. Reverse MR analysis indicated that chronic periodontitis could alter the levels of 47 blood metabolites. Pathway analysis revealed that chronic periodontitis might affect blood metabolite levels through four pathways: vitamin B6 metabolism, ether lipid metabolism, glycerophospholipid metabolism and caffeine metabolism. This study provides new insights into the pathogenesis of periodontitis, identifying potential blood biomarkers for early detection and monitoring.

Pulp stones (PS) are incidental, mostly asymptomatic, radiographic findings that may hinder endodontic therapy. They are observed as radiopaque aggregates within coronal or radicular pulp tissue on intraoral periapical, bite-wing, panoramic radiographs and cone-beam computed tomography images. This study aimed to evaluate PS prevalence in patients with cardiovascular disease (CVD), diabetes mellitus (DM), and chronic periodontitis (CP) as compared with controls, as a function of age and sex. This cross-sectional study included 200 subjects: 50 healthy controls, and 50 patients each with CVD, DM, and CP. All participants underwent digital panoramic radiograph (orthopantomogram) (OPG) evaluation for the presence/absence, number, and location of PS. Significant differences in PS prevalence were observed among the groups (P<0.01), with CVD patients showing the highest prevalence. Older individuals (>50 years) and first molars were most frequently affected. The maxillary arch showed a significantly higher prevalence than the mandible (odds ratio [OR]=1.45; 95% CI 1.22-1.72). The strongest risk factor was CVD (OR=7.38; 95% CI 5.20-10.47), followed by DM (OR=4.18; 95% CI 2.91-5.99) and CP (OR=4.16; 95% CI 2.88-6.00). Age was significantly associated with PS, while sex showed no association. The presence of PS, even among healthy controls, may serve as an adjunctive radiographic marker and could also alert dental practitioners to the possibility of underlying systemic disease.

Background. Chronic apical periodontitis is an inflammatory disease associated with infection of the root canal and represents a major challenge in dentistry. Its prevalence is rapidly increasing among the adult population. The condition is characterized by variability in inflammatory responses and bone resorption. Genetic factors play a central role in its pathogenesis. Single-nucleotide polymorphisms (SNPs) significantly affect gene expression and protein activity. Recent studies highlight the importance of integrating genetic data into clinical dentistry. Objective. To determine the role of intergenic associations of key genes involved in the modulation of inflammatory and immune responses in hereditary predisposition to chronic apical periodontitis. Methods. A prospective single-center case control study was conducted from November 2024 to April 2025 at the Yaroslavl State Medical University (Ministry of Health of the Russian Federation) and the Medical Center for Diagnostics and Prevention “Sodruzhestvo.” The study involved 200 participants: 150 patients with chronic apical periodontitis and 50 healthy controls. The diagnosis was confirmed clinically and radiographically. Single-nucleotide polymorphisms of eight genes (IL-10, IL-1β, TNF-α, GSTP1, CYP1A2, TP53, COL1A1, and MMP-9) were analyzed using real-time polymerase chain reaction (PCR). Statistical analysis was performed using JMP Pro v.18.0 (SAS Institute Inc., https://www.jmp.com, 2024), Haplostats v.1.9.7 (Schaid, D.J., &amp; Sinnwell, J.P., Software for haplotype-based association analysis, USA), and MDR v.3.0.2 (Multifactor Dimensionality Reduction, SourceForge, USA). The optimal models were identified based on the highest cross-validation consistency (CVC) and lowest testing balanced accuracy error. The significance level was set at p &lt; 0.05. Results. MDR analysis revealed significant intergenic interactions associated with the development of chronic apical periodontitis. The three-locus model IL-1β×TNF-α×MMP-9 demonstrated the highest predictive value (balanced accuracy 79.8%, cross-validation consistency 10/10), highlighting the synergistic effect of inflammatory cytokines and proteolytic processes. Hardy–Weinberg equilibrium analysis showed deviations for CYP1A2 and TP53 in the chronic apical periodontitis group, suggesting an influence of environmental factors. The Fruchterman—Reingold graph confirmed a strong interaction between IL-1β and TNF-α, whereas COL1A1 displayed a moderate association. These findings indicate the multigenic nature of predisposition to chronic apical periodontitis and enable personalized diagnostics and therapy based on the combined genetic effects. Conclusion. The results of this study may lay a foundation for developing personalized diagnostic and treatment strategies that account for individual genetic profiles. Integrating such approaches into clinical practice could improve disease outcome prediction, optimize therapeutic interventions, and reduce the risk of complications related to the pathological process.

Background. Current advances in digital dentistry enhance the efficiency of rehabilitation for patients with missing teeth, while gradually replacing analog methods. The combination of cone beam computed tomography with intraoral scan data allows for precise virtual planning of surgical procedures thus minimizing deviations during implant placement. Furthermore, high precision in the placement of prosthetic structures is ensured. In this article, a clinical case study is presented to demonstrate a full digital protocol, which is becoming increasingly relevant in dental practice. Clinical case description. This clinical case study reports on the total rehabilitation of a patient’s maxillary teeth. The cause of tooth loss was chronic periodontitis and its complications. After examination, the patient was diagnosed with ICD-10: K08.1: Loss of teeth due to accident, extraction, or local periodontal disease; K05.3: Chronic periodontitis. Tooth 1.3 was extracted, six implants were placed using a navigation template, superstructures (multi-unit abutments) were installed, followed by intraoral scanning of the jaws to make a temporary prosthetic structure. On Day 3 after surgery, a temporary structure was fixed in the oral cavity. After six months, a repeat intraoral scan was performed; a permanent screw-fixed prosthesis made of zirconium dioxide (without titanium bases) was prepared. Conclusion. The clinical case described demonstrates a well-established approach to total maxillary rehabilitation using dental implants and a fully digital protocol. Digital technologies contribute to improving the effectiveness of implant treatment for patients, reducing the risk of complications, increasing patient comfort, and facilitating communication between the dentist and dental technician.

Metalloimmunotherapies are emerging as promising treatment for cancer and infectious diseases by harnessing immune responses involving metal ions. However, their potential role in tissue regeneration remains unclear. In the context of chronic periodontitis, an inflammatory disease characterized by accumulated inflammatory cells and progressive alveolar bone loss, we report new effects of copper on inflammatory resolution and alveolar bone regeneration by enhancing lymphatic drainage. We first construct an injectable and thermosensitive hydrogel using catechol-conjugated chitosan (CHI-C) and pluronic F-127 (PF-127) to enhance the adhesive capacity of nanocomposite. Then, copper-containing mesoporous bioactive glass nanoparticles (Cu-BGs) are fabricated for sustained release of copper ions in acidic environments and mixed with VEGFC (a growth factor increasing lymphangiogenesis) into the hydrogel (Cu/VEGFC@Hy). We confirm the in vitro impact of copper on proliferation and migration of lymphatic endothelial cells (LECs) and smooth muscle cells (SMCs), key components of collecting lymphatic vessels. RNA-seq analysis reveals that copper promotes proliferation in LECs and SMCs by targeting COX4i2/ERK pathway. In periodontitis model, Cu/VEGFC@Hy significantly improves the reconstruction of collecting lymphatic vessels, accelerating lymphatic drainage and rejuvenating alveolar bone mass. Overall, the well-designed Cu/VEGFC@Hy effectively reduces inflammatory accumulation by promoting lymphatic vessel formation and tissue regeneration in inflammatory diseases. STATEMENT OF SIGNIFICANCE: This study introduces a pioneering metalloimmunotherapy approach for chronic periodontitis, utilizing copper ions to enhance lymphatic drainage and alveolar bone regeneration. We developed an injectable, thermosensitive hydrogel incorporating copper-containing mesoporous bioactive glass nanoparticles and VEGFC, which synergistically promotes the reconstruction of collecting lymphatic vessels and reduces inflammatory accumulation. Our findings reveal a novel mechanism where copper ions stimulate the proliferation and migration of lymphatic endothelial and smooth muscle cells via the COX4i2/ERK pathway. This work not only offers a promising biomaterial-based therapy for periodontitis but also broadens the application of metal ions in tissue engineering and regenerative medicine, with potential implications for other inflammatory diseases.

Water-responsive materials represent a class of stimuli-responsive "smart" materials that have become a focal point of recent research in recent years. Their unique ability to undergo reversible shape changes in response to water or humidity makes them highly versatile for various applications. Inspired by natural phenomena such as the hygroscopic movements of plant fibers and the supercontraction of spider silk, these materials exhibit excellent shape adaptability, phase transition, and wet tissue adhesion capabilities. Their ability to thrive in the aqueous environment, where saliva and gingival crevicular fluid provide a dynamic medium, makes them particularly promising for applications in oral medicine. This review, drawing on literature primarily from the past decade, comprehensively discusses the mechanisms, building blocks, and current advancements in water-responsive materials, with a focus on their potential in oral drug delivery, tissue engineering, and wound management. Key applications include alveolar bone regeneration, chronic wound healing, periodontitis treatment, and hemostatic dressings, where their shape adaptability, biocompatibility, and biodegradability address critical clinical challenges. Despite their potential, the application of water-responsive materials in oral medicine remains underexplored, highlighting the need for further research to optimize their design and functionality. By integrating insights from recent studies, this review aims to provide a foundation for the development of next-generation water-responsive materials tailored to meet the unique demands of oral healthcare.

Subject. The microbial composition of the root canal contents in patients with chronic apical periodontitis was investigated, differentiated by the clinical course of the disease. Objectives. To identify and compare the microbial species composition in root canals of patients with asymptomatic and symptomatic chronic apical periodontitis, using highly sensitive molecular genetic analysis methods. Methodology. The study was conducted based on Yaroslavl State Medical University and Sodruzhestvo LLC. It was a single-center, prospective, case-control study that randomly divided patients with chronic apical periodontitis into two groups: asymptomatic (n=170) and symptomatic (n=130). Before endodontic treatment, the contents of the root canals were collected under sterile conditions using a cofferdam, an apex locator, and endocanal paper pins. DNA was isolated at an automated station and then analyzed for microorganisms using real-time polymerase chain reaction with specific reagent kits. To identify key pathogens, the detection rate of microorganisms was compared between the two groups using the Yates-adjusted χ² criterion and the exact Fisher criterion with a significance level of p &lt; 0.05 for statistical analysis. Results. The polymerase chain reaction (PCR) method was used to detect microorganisms, allowing for the identification of even small species. Statistical analysis confirmed the significance of the differences between groups. The results showed that symptomatic patients have a higher detection rate of highly virulent pathogens, such as E. faecalis and F. nucleatum, and their synergistic association contributes to the formation of resistant biofilms. Asymptomatic patients, on the other hand, are dominated by streptococci and form a more balanced community. Conclusion. These findings open up new possibilities for personalized endodontic treatment based on a patient's microbiological profile.

AimThis randomized controlled trial aimed to assess the efficacy of a combined Nd:YAG laser and bioactive glass (BAG) for dentin hypersensitivity following scaling and root planning (SRP). The study compared various desensitization protocols and evaluated the time-dependent effects of immediate desensitization therapy post-SRP.Methods80 patients with chronic periodontitis (200 sensitive teeth) were randomly assigned to five groups: group A (BAG), group B (Nd:YAG laser), group C (Nd:YAG laser + BAG), group D (BAG + Nd:YAG laser), and group E (control). Hypersensitivity was assessed via air-blast stimulation and measured on a Visual Analogue Scale (VAS) at baseline (T0), immediately after intervention (T1), and at 1-, 4-, and 8-week (T2–T4) post-treatment. Between-group comparisons of baseline characteristics and post-treatment measurements were analyzed with one-way ANOVA. Longitudinal comparisons across timepoints were evaluated using repeated-measures ANOVA. Categorical variables were compared by chi-square test.ResultsNo significant differences in demographic characteristics or baseline VAS scores were observed across the groups before treatment (P > 0.05). All interventional groups (A–D) showed significant and sustained reductions in VAS scores relative to both baseline and control (all P < 0.001), with group D achieving the greatest improvement at T4 (2.00 ± 0.68, P < 0.05 vs. group C). Effectiveness rates were also significantly higher in groups A–D than in group E (all P < 0.001). Combination therapies (C and D) proved superior to monotherapies (A and B), with group D maintaining the highest effectiveness rate through T4 (92.5%). A gradual decline in effectiveness was observed over time, being least pronounced in group D.ConclusionsThe combined application of BAG and Nd:YAG laser therapy demonstrated a significant reduction in dentin hypersensitivity post-SRP, exhibiting superior and sustained efficacy compared to monotherapies. Furthermore, the sequential treatment involving BAG applied prior to Nd:YAG laser irradiation showed the most pronounced therapeutic effect in symptom alleviation.

Although widely used in periodontal research, rodents are naturally resistant to periodontitis. Conventional models, such as ligature-induced periodontitis, often fail to sustain defects due to spontaneous tissue regeneration after ligature removal. To address this, we refined a rat ligature-induced model of experimental periodontitis to better mimic the chronic, progressive nature of human periodontitis. As a first step, following a split-mouth design, we compared the effectiveness of 3/0 silk thread and 0.008-inch orthodontic wire as ligature materials. Ligatures were applied around the left mandibular first molar for 6, 10, and 14 days. Periodontal pocket irrigation was performed every second day using a suspension of P. gingivalis, P. intermedia, and S. gordonii. As a second step, we evaluated whether silk-ligature alone, without human periopathogens, would be sufficient to induce a stable and progressive periodontal lesion. For that purpose, a silk ligature was removed on day 14, and the bone defect dynamics were monitored at 14-, 21-, and 28-days post-removal using micro-CT. Both wire and silk ligatures, in combination with bacterial irrigation, effectively induced rapid interproximal alveolar bone loss. However, silk ligature only, without periodontopathogen colonization, resulted in significantly lower bone loss (1.076 ± 0.22 mm vs. 2.012 ± 0.374 mm; p = 0.003) and the induced alveolar bone defects gradually resolved again over time. The proposed rat model of periodontitis is well characterized and replicates human disease by sustaining colonization with viable periopathogens, leading to progressive disease with alveolar bone loss. The suggested model is straightforward, easy to establish and can be used reliably in preclinical studies.

Aim. This study aimed to investigate whether chronic apical periodontitis (CAP) is influenced not only by microbial infection but also by systemic biomarkers, lifestyle, and dietary patterns. Methods. An observational cross-sectional design was applied on a cohort of adult patients, who underwent radiographic diagnosis, blood and saliva collection for oxidative stress and advanced glycation end products (AGEs) analysis, and also completed structured dietary and lifestyle questionnaires. Results. Biochemical analyses revealed no significant differences in oxidative stress or advanced glycation end products between CAP and non-CAP groups, suggesting that systemic markers may not adequately reflect localized periapical inflammation. Similarly, smoking habits and physical activity did not show relevant associations with disease presence. By contrast, diet emerged as a significant determinant. Higher consumption of fried potatoes, refined products such as croissants and white rice, and acidic fruits like oranges was associated with increased risk of CAP. Conversely, regular consumption of breakfast cereals demonstrated a protective effect, reducing disease likelihood. These associations were confirmed in multivariate analysis, highlighting the independent role of specific dietary patterns. Conclusion. CAP appears to be shaped not only by infection but also by everyday nutrition, with fried and acidic foods favoring disease, while wholegrain cereals provide resilience. These findings emphasize the importance of integrating nutritional guidance into dental care to complement conventional endodontic therapy.

Comparison of the Efficacy of Adjunctive Aids After Scaling and Root Planing in Patients With Chronic Periodontitis

This study aimed to elucidate the role of peroxisome proliferator-activated receptor-γ (PPAR-γ) in regulating macrophage efferocytosis during the pathogenesis of chronic apical periodontitis (CAP). Clinical specimens, rat periapical lesion models, and an in vitro model simulating the CAP inflammatory milieu were employed to examine the contribution of PPAR-γ to efferocytosis throughout disease progression. The expression of PPAR-γ in vivo was assessed by single-cell RNA sequencing and immunohistochemical (IHC) staining. Pearson’s correlation and linear trend tests were conducted to investigate the association between PPAR-γ and macrophage efferocytosis during CAP progression. Pharmacological modulation of PPAR-γ was further conducted using rosiglitazone (RSG) as an agonist and GW9662 as an antagonist, followed by an assessment of efferocytosis-related parameters and inflammatory responses. Both clinical specimens and animal models demonstrated a progressive reduction in PPAR-γ expression and macrophage efferocytosis during CAP. Notably, PPAR-γ attenuated efferocytosis impairment and significantly reduced pathogen-induced inflammatory responses in macrophages. These findings indicate that defective macrophage efferocytosis contributes to the exacerbation of CAP severity, whereas targeting PPAR-γ may represent a promising therapeutic strategy to alleviate inflammation in periapical lesions by restoring efferocytic capacity. Collectively, this study highlights PPAR-γ as a potential therapeutic target warranting further investigation in CAP treatment.

Chronic apical periodontitis (CAP), an inflammatory disease of periapical tissues, leads to alveolar bone destruction. Current therapies lack osteoblast-targeting specificity and fail to effectively promote bone repair. Extracellular vesicles (EVs), particularly milk-derived EVs (MEVs), show potential for bone regeneration and have anti-inflammatory effects. We investigated the therapeutic potential of engineered MEVs modified with the osteoblast-targeting peptide DSPE-PEG-Mal-Cys-SDSSD (DPS) in CAP. DPS-MEVs enhanced osteogenic capacity and exhibited greater osteoblast targeting compared with unmodified MEVs through oxidative phosphorylation (OXPHOS) activation, driven by Kruppel-like factor 4 (KLF4)-mediated upregulation of NADH dehydrogenase 1 alpha subcomplex 4 (Ndufa4) in vivo and in vitro. We also transplanted DPS-MEVs into a CAP model of dogs through apical microsurgery and found that DPS-MEVs enhanced bone repair and reduced inflammation by promoting polarization of M2 macrophages. These findings highlighted the potential of engineered DPS-MEVs as a dual-functional therapy for CAP, combining immunomodulation and tissue repair to advance precision treatment for inflammatory bone diseases.

The intricate shared genetic architecture underlying halitosis and its related disorders—including salivary secretion disorders, chronic periodontitis, gastroesophageal reflux disease, dental caries, chronic sinusitis, helicobacter pylori infection, and porphyromonas genus abundance—remains incompletely characterized. Our study employed genomic structural equation modeling (Genomic SEM) to define the halitosis common factor (HCF) representing the shared genetic architecture of halitosis-related disorders. Coupled with diverse post-GWAS analytical methods, we aimed to discover susceptible loci and investigate genetic associations with external traits. Furthermore, we explored enriched genetic pathways, cellular layers, and genomic elements. Polygenic risk score analyses, leveraging our integrated GWAS data, were conducted to assess chromosomal-level risk associations for the HCF. A well-fitted genomic SEM integrated GWAS data, revealing the shared genetic architecture of halitosis-related disorders. We identified 23 independent genome-wide significant SNP loci, all previously unreported for this HCF relative to the input single-trait GWAS. Fine-mapping of variants and gene prioritization pinpointed numerous high-confidence putative causal variants and candidate susceptible genes. Subsequent analyses further illuminated the shared genetic architecture underlying HCF and multiple external traits, notably neuropsychiatric characteristics, cognitive function, and inflammatory or metabolic conditions. Notably, this study presents the first comprehensive genetic characterization of halitosis and its related disorders through a GWAS analysis of an unmeasured composite phenotype, providing novel insights into shared etiological pathways potentially linking oral health to systemic factors across these conditions.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-20316-y.