ABSTRACT
Observational studies suggest that child maltreatment increases the risk of externalizing spectrum disorders such as attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), antisocial personality disorder (ASPD), and substance use disorder (SUD). Yet, only few of such associations have been investigated by approaches that provide strong evidence for causation, such as Mendelian Randomization (MR). Establishing causal inference is essential given the growing recognition of gene-environment correlations, which can confound observational research in the context of childhood maltreatment. Evaluating causality between child maltreatment and the externalizing phenotypes, we used genome-wide association study (GWAS) summary data for child maltreatment (143,473 participants), ADHD (20,183 cases; 35,191 controls), CD (451 cases; 256,859 controls), ASPD (381 cases; 252,877 controls), alcohol use disorder (AUD; 13,422 cases; 244,533 controls), opioid use disorder (OUD; 775 cases; 255,921 controls), and cannabinoid use disorder (CUD; 14,080 cases; 343,726 controls). We also generated a latent variable 'common externalizing factor' (EXT) using genomic structural equation modeling. Genetically predicted childhood maltreatment was consistently associated with ADHD (odds ratio [OR], 10.09; 95%-CI, 4.76-21.40; P = 1.63 × 10-09), AUD (OR, 3.72; 95%-CI, 1.85-7.52; P = 2.42 × 10-04), and the EXT (OR, 2.64; 95%-CI, 1.52-4.60; P = 5.80 × 10-04) across the different analyses and pleiotropy-robust methods. A subsequent GWAS on childhood maltreatment and the externalizing dimension from Externalizing Consortium (EXT-CON) confirmed these results. Two of the top five genes with the strongest associations in EXT GWAS, CADM2 and SEMA6D, are also ranked among the top 10 in the EXT-CON. The present results confirm the existence of a common externalizing factor and an increasing vulnerability caused by child maltreatment, with crucial implications for prevention. However, the partly diverging results also indicate that specific influences impact individual phenotypes separately.
ABSTRACT
PURPOSE: Despite the multiprofessional concept surrounding palliative care patients (PCPs) and their high prevalence of oral issues, licensed dentists (LDs) are often not included in their treatment team. This study aimed to examine the current state of cooperation and to determine whether and how LDs should be included in the care for PCPs. METHODS: This single-centre cross-sectional study was conducted at the University Hospital Muenster, Germany. We surveyed three participant groups: PCPs, LDs, and healthcare professionals (HCPs). Questionnaires were tailored for each group, with some questions common for comparison. RESULTS: The study encompassed the results of 48 questionnaires from LDs, 50 from PCPs along with 50 from HCPs. Consensus was reached among all parties (LDs: 73% (n = 35/48); HCPs: 94%, n = 47/50; PCPs: 60%, n = 30/50) that involving LDs in the treatment concept is favourable. On the other hand, a significant discrepancy emerged in the perception of the dental treatment effort required by PCPs. While LDs (81%; n = 39/48) and HCPs (64%; n = 32/50) were convinced of increased effort, PCPs (34%; n = 17/50) largely did not share this perspective. To enhance patient care and formulate appropriate treatment plans, LDs consider both training (58%; n = 28/48) and guidebooks (71%; n = 34/48) to be valuable and would attend or use such resources. CONCLUSION: This study sheds light on the current gaps in including LDs in palliative care teams and emphasizes the importance of multidisciplinary collaboration to address oral health needs effectively. Development of continuing education options and collaborative models between LDs and HCPs needs to be further expanded in future.
Subject(s)
Health Personnel , Palliative Care , Humans , Palliative Care/methods , Cross-Sectional Studies , Health Personnel/education , Surveys and Questionnaires , DentistsABSTRACT
AIM: To estimate association between the use of interdental cleaning aids (IDAs) and type on 7-year follow-up levels of interdental plaque, interdental gingival inflammation, interdental periodontitis severity, the number of interdental sound surfaces and the number of missing teeth in a population-based cohort study. MATERIALS AND METHODS: We used 7-year follow-up data of 2224 participants from the Study of Health in Pomerania (SHIP-TREND). We applied generalized linear and ordinal logistic models, adjusting for confounding and selection bias using inverse probability treatment weighting and multiple imputation. RESULTS: Flossers were 32% less likely to have higher interdental plaque (iPlaque) levels than non-users of IDAs (odds ratio [OR] = 0.68; 95% confidence interval [CI]: 0.50-0.94); flossing resulted in 5% lower means of iPlaque. Effects on interdental bleeding on probing (iBOP), mean interdental probing depths and mean interdental clinical attachment levels were direction-consistent but statistically non-significant. Interdental brushing was associated with lower follow-up levels for interdental plaque (OR = 0.73; 95% CI: 0.57-0.93) and iBOP (OR = 0.69; 95% CI: 0.53-0.89). IDAs were more effective in reducing iPlaque in participants with periodontitis, whereas iBOP reduction was more pronounced in participants with no or mild periodontitis. The analyses did not suggest that the use of IDAs affected caries. Finally, applying change score analyses, flossing reduced tooth loss incidence (incidence rate ratio [IRR] = 0.71) compared with non-users of IDAs. CONCLUSIONS: Recommending flossing and interdental brushing in dental practices represents an approach to the prevention of gingivitis and consequently periodontitis.
Subject(s)
Dental Plaque , Gingivitis , Periodontitis , Tooth Loss , Humans , Oral Health , Dental Devices, Home Care , Cohort Studies , Toothbrushing , Periodontitis/epidemiology , Periodontitis/prevention & control , Gingivitis/epidemiology , Gingivitis/prevention & control , Dental Plaque/epidemiology , Dental Plaque/prevention & control , Dental Plaque IndexABSTRACT
AIM: Evidence from a Phase IIa trial showed that a complement C3-targeted drug reduced gingival inflammation in patients with gingivitis. Using drug-target Mendelian randomization (MR), we investigated whether genetically proxied C3 inhibition alters the risk of periodontitis. MATERIALS AND METHODS: We used multiple 'cis' instruments from the vicinity of the encoding loci of C3. Instrument selection was restricted to the drug target encoding loci (chromosome 19; 6,677,715-6,730,573 (GRCh37/hg19)). We selected three uncorrelated single-nucleotide polymorphisms (rs141552034, rs145406915, rs11569479) that were associated with serum C3 levels (p value <1 × 10-4 ) from a genome-wide association study (GWAS) of 5368 European descent individuals. We extracted association statistics from a GWAS of 17,353 clinical periodontitis cases and 28,210 European controls. Wald ratios were combined using inverse-variance weighted meta-analysis to estimate the odds ratio (OR) of the genetically proxied inhibition of C3 in relation to periodontitis. RESULTS: MR analysis revealed that the inhibition of C3 reduces the odds of periodontitis (OR 0.91 per 1 standard deviation reduction in C3; 95% confidence interval 0.87-0.96, p value = .0003). CONCLUSIONS: Findings from our MR analysis suggest a potential protective effect of C3 blockade against periodontitis.
Subject(s)
Gingivitis , Periodontitis , Humans , Clinical Trials, Phase II as Topic , Complement C3/genetics , Genome-Wide Association Study , Mendelian Randomization Analysis , Periodontitis/drug therapy , Periodontitis/genetics , Polymorphism, Single NucleotideABSTRACT
Periodontitis (PD), a widespread chronic infectious disease, compromises oral health and is associated with various systemic conditions and hematological alterations. Yet, to date, it is not clear whether serum protein profiling improves the assessment of PD. We collected general health data, performed dental examinations, and generated serum protein profiles using novel Proximity Extension Assay technology for 654 participants of the Bialystok PLUS study. To evaluate the incremental benefit of proteomics, we constructed two logistic regression models assessing the risk of having PD according to the CDC/AAP definition; the first one contained established PD predictors, and in addition, the second one was enhanced by extensive protein information. We then compared both models in terms of overall fit, discrimination, and calibration. For internal model validation, we performed bootstrap resampling (n = 2000). We identified 14 proteins, which improved the global fit and discrimination of a model of established PD risk factors, while maintaining reasonable calibration (area under the curve 0.82 vs 0.86; P < 0.001). Our results suggest that proteomic technologies offer an interesting advancement in the goal of finding easy-to-use and scalable diagnostic applications for PD that do not require direct examination of the periodontium.
Subject(s)
Periodontitis , Proteomics , Humans , Proteomics/methods , Periodontitis/diagnosis , Risk Factors , Blood ProteinsABSTRACT
BACKGROUND: Observational studies indicate a relationship between vitamin D (25-hydroxyvitamin D; 25OHD) deficiency and the development of internalising disorders, especially depression. However, causal inference approaches (e.g. Mendelian randomisation) did not confirm this relationship. Findings from biobehavioural research suggests that new insights are revealed when focusing on psychopathological dimensions rather than on clinical diagnoses. This study provides further evidence on the relationship between 25OHD and the internalising dimension. AIMS: This investigation aimed at examining the causality between 25OHD and internalising disorders including a common internalising factor. METHOD: We performed a two-sample Mendelian randomisation using genome-wide association study (GWAS) summary data for 25OHD (417 580 participants), major depressive disorder (45 591 cases; 97 674 controls), anxiety (5580 cases; 11 730 controls), post-traumatic stress disorder (12 080 cases; 33 446 controls), panic disorder (2248 cases; 7992 controls), obsessive-compulsive disorder (2688 cases; 7037 controls) and anorexia nervosa (16 992 cases; 55 525 controls). GWAS results of the internalising phenotypes were combined to a common factor representing the internalising dimension. We performed several complementary analyses to reduce the risk of pleiotropy and used a second 25OHD GWAS for replication. RESULTS: We found no causal relationship between 25OHD and any of the internalising phenotypes studied, nor with the common internalising factor. Several pleiotropy-robust methods corroborated the null association. CONCLUSIONS: Following current transdiagnostic approaches to investigate mental disorders, our results focused on the shared genetic basis between different internalising phenotypes and provide no evidence for an effect of 25OHD on the internalising dimension.
Subject(s)
Depressive Disorder, Major , Humans , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/epidemiology , Depressive Disorder, Major/genetics , Genome-Wide Association Study , Mendelian Randomization Analysis/methods , Vitamin D/genetics , Polymorphism, Single NucleotideABSTRACT
AIM: Previous studies on the association between proton pump inhibitor (PPI) intake and the increased risk of dementia has shown discrepancies in their conclusions. We aimed to provide updated evidence based on extensive bias assessments and quantitative sensitivity analyses. METHODS: We searched the databases PubMed, EMBASE, SCOPUS, CENTRAL and clinicaltrials.gov for prospective studies that examined an association between PPI use and dementia, up to February 2022. Each study was assessed using the Cochrane risk of bias assessment tools for non-randomized studies of interventions (ROBINS-I) or randomized trials (RoB2). Pooled risk ratios (RRs) and 95% prediction intervals were computed using random-effects models. Sensitivity analyses were adjusted for small-study bias. RESULTS: We included nine observational studies with 204 108 dementia cases in the primary analysis on the association between PPI use vs. non-use and dementia, and the RR was 1.16 (95% CI = 1.00; 1.35). After adjusting for small-study bias by Copas selection model and Rücker's shrinkage procedure, the RR was 1.16 (1.02; 1.32) and 1.15 (1.13; 1.17), respectively. A subgroup analysis of PPI use vs. non-use regarding Alzheimer's disease risk yielded an RR of 1.15 (0.89; 1.50). The secondary analysis on the risk of dementia by use of PPI vs. histamine-2 receptor antagonist showed an RR of 1.03 (0.66; 1.62). CONCLUSION: This meta-analysis provided no clear evidence for an association between PPI intake and the risk of dementia. Due to discrepancies in sensitivity analyses, however, some risk of dementia by PPI use cannot be ruled out. Since an unequivocal conclusion is still pending, further research is warranted.
Subject(s)
Dementia , Proton Pump Inhibitors , Humans , Proton Pump Inhibitors/adverse effects , Prospective Studies , Bias , Histamine H2 Antagonists/adverse effects , Dementia/chemically induced , Dementia/epidemiologyABSTRACT
PURPOSE: Examining epigenetic patterns is a crucial step in identifying molecular changes of disease pathophysiology, with DNA methylation as the most accessible epigenetic measure. Diet is suggested to affect metabolism and health via epigenetic modifications. Thus, our aim was to explore the association between food consumption and DNA methylation. METHODS: Epigenome-wide association studies were conducted in three cohorts: KORA FF4, TwinsUK, and Leiden Longevity Study, and 37 dietary exposures were evaluated. Food group definition was harmonized across the three cohorts. DNA methylation was measured using Infinium MethylationEPIC BeadChip in KORA and Infinium HumanMethylation450 BeadChip in the Leiden study and the TwinsUK study. Overall, data from 2293 middle-aged men and women were included. A fixed-effects meta-analysis pooled study-specific estimates. The significance threshold was set at 0.05 for false-discovery rate-adjusted p values per food group. RESULTS: We identified significant associations between the methylation level of CpG sites and the consumption of onions and garlic (2), nuts and seeds (18), milk (1), cream (11), plant oils (4), butter (13), and alcoholic beverages (27). The signals targeted genes of metabolic health relevance, for example, GLI1, RPTOR, and DIO1, among others. CONCLUSION: This EWAS is unique with its focus on food groups that are part of a Western diet. Significant findings were mostly related to food groups with a high-fat content.
Subject(s)
Epigenome , Genome-Wide Association Study , Male , Middle Aged , Humans , Female , Epigenome/genetics , CpG Islands , Epigenesis, Genetic , DNA MethylationABSTRACT
AIM: Epidemiological and pre-clinical studies suggest a chemoprotective role of lipid-lowering agents in periodontitis. We tested the association of genetically proxied inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), Niemann-Pick C1-Like 1 (NPC1L1) and proprotein convertase subtilisin/kexin type 9 (PCSK9) with periodontitis. MATERIALS AND METHODS: Genetic variants in HMGCR, NCP1L1 and PCSK9 associated with low-density lipoprotein (LDL) cholesterol in a genome-wide association study (GWAS) meta-analysis (N = 188,578) were used to proxy therapeutic inhibition of HMGCR, NPC1L1 and PCSK9. For these genetic variants, associations with periodontitis were obtained from GWAS of 17,353 cases and 28,210 controls in the GeneLifestyle Interactions in Dental Endpoints consortium. Generalized weighted least squares analysis accounted for linkage disequilibrium of genotypes to derive pooled estimates. RESULTS: While genetically proxied HMGCR inhibition equivalent to 1 mmol/L reduction in LDL was not associated with odds of periodontitis (odds ratio [OR] = 0.92 [95% confidence interval [CI]: 0.73; 1.16]; p = .4905; false discovery rate [FDR] = 0.4905), genetically proxied NPC1L1 (OR = 0.53 [95% CI: 0.35; 0.81]; p = .0038; FDR = 0.0077) and PCSK9 (OR = 0.84 [95% CI: 0.74; 0.95]; p = .0051; FDR = 0.0077) inhibition lowered the odds of periodontitis. CONCLUSIONS: Genetically proxied inhibition of NCP1L1 and PCSK9 was associated with lower odds of periodontitis.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , PCSK9 Inhibitors , Periodontitis , Humans , Cholesterol, LDL , Genome-Wide Association Study , Genotype , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Membrane Transport Proteins/genetics , Periodontitis/genetics , Periodontitis/drug therapy , Proprotein Convertase 9/genetics , PCSK9 Inhibitors/therapeutic useABSTRACT
BACKGROUND: Observational research suggests that vitamin D levels affect psoriasis. However, observational studies are prone to potential confounding or reverse causation, which complicates interpreting the data and drawing causal conclusions. AIM: To apply Mendelian randomization (MR) methods to comprehensively assess a potential association between vitamin D and psoriasis. METHODS: Genetic variants strongly associated with 25-hydroxyvitamin D (25OHD) in genome-wide association study (GWAS) data from 417 580 and 79 366 individuals from two independent studies served as instrumental variables (used as the discovery and replication datasets, respectively). As the outcome variable, we used GWAS data of psoriasis (13 229 people in the case group, 21 543 in the control group). We used (i) biologically validated genetic instruments, and (ii) polygenic genetic instruments to assess the relationship between genetically proxied vitamin D and psoriasis. We carried out inverse-variance weighted (IVW) MR analyses for the primary analysis. In sensitivity analyses, we used robust MR approaches. RESULTS: MR analyses of both the discovery and replication datasets did not show an effect of 25OHD on psoriasis. Neither the IVW MR analysis of the biologically validated instruments [discovery dataset: odds ratio (OR) 0.99; 95% confidence interval (CI) 0.88-1.12, P = 0.873; replication dataset: OR 0.98, 95% CI 0.66-1.46, P = 0.930] nor that of the polygenic genetic instruments (discovery dataset: OR 1.00, 95% CI 0.81-1.22, P = 0.973; replication dataset: OR 0.94, 95% CI 0.64-1.38, P = 0.737) revealed an impact of 25OHD on psoriasis. CONCLUSION: The present MR study did not support the hypothesis that vitamin D levels, measured by 25OHD, affect psoriasis. This study was conducted on Europeans, so the conclusions may not be applicable to all ethnicities.
Subject(s)
Mendelian Randomization Analysis , Psoriasis , Humans , Risk Factors , Mendelian Randomization Analysis/methods , Genome-Wide Association Study , Vitamin D , Vitamins , Psoriasis/genetics , Polymorphism, Single NucleotideABSTRACT
OBJECTIVES: Observational studies suggested an inverse association between physical activity and periodontitis. However, observational studies might be subject to unobserved confounding and reverse causation bias. We conducted an instrumental variable study to strengthen the evidence on the relationship between physical activity and periodontitis. MATERIALS AND METHODS: We used genetic variants associated with self-reported and accelerometer-assessed physical activity in 377,234 and 91,084 UK Biobank participants, respectively, as instruments. For these instruments, genetic associations with periodontitis were obtained from 17,353 cases and 28,210 controls in the GeneLifestyle Interactions in Dental Endpoints consortium. RESULTS: We found no evidence for effects of self-reported moderate-to-vigorous physical activity, self-reported vigorous physical activity, accelerometry "average accelerations," and "fraction of accelerations > 425 milli-gravities" on periodontitis. For example, the odds ratio for self-reported moderate-to-vigorous physical activity was 1.07 (95% credible interval: 0.87; 1.34) in Causal Analysis using Summary Effect Estimates. We conducted sensitivity analyses to rule out weak instrument bias and correlated horizontal pleiotropy. CONCLUSIONS: The study does not support an effect of physical activity on the risk of periodontitis. CLINICAL RELEVANCE: This study provides little evidence that recommending physical activity would help prevent periodontitis.
Subject(s)
Mendelian Randomization Analysis , Periodontitis , Humans , Self Report , Exercise , Periodontitis/epidemiology , Accelerometry , Genome-Wide Association Study , Polymorphism, Single NucleotideABSTRACT
OBJECTIVES: Periodontitis (PD) can cause systematic inflammation and is associated with various metabolic processes in the body. However, robust serum markers for these relationships are still lacking. This study aims to identify novel circulating inflammation-related proteins associated with PD using targeted proteomics. MATERIALS AND METHODS: We used population-based, cross-sectional data from 619 participants of the Polish Longitudinal University Study (Bialystok PLUS). Mean pocket probing depth (mPPD) and proportion of bleeding on probing (pBOP) served as exposure variables. Fifty-two inflammation-related proteins were measured using the Olink Target 96 Cardiovascular III and the Olink Target 96 Immune Response panels. Associations between periodontal measures and proteins were tested using covariate-adjusted linear regression models. RESULTS: At a false discovery rate of < 0.05, we identified associations of mPPD and pBOP with platelet-endothelial cell adhesion molecule-1 (PECAM-1) and tripartite motif-containing protein 21 (TRIM21). CONCLUSION: This study revealed novel associations between PD and serum levels of PECAM-1 and TRIM21. Our results suggest that these proteins might be affected by molecular processes that take place in the inflamed periodontium. CLINICAL RELEVANCE: Novel associations of PECAM-1 and TRIM21 with PD indicate promising serum markers for understanding the disease's pathophysiological processes and call for further biomedical investigations.
Subject(s)
Periodontitis , Proteomics , Humans , Platelet Endothelial Cell Adhesion Molecule-1 , Cross-Sectional Studies , C-Reactive Protein/analysis , Inflammation , Periodontitis/complications , BiomarkersABSTRACT
BACKGROUND AND PURPOSE: Understanding the adverse effects of proton pump inhibitors (PPIs) is important due to their widespread use, but the available evidence for an increased dementia risk amongst patients taking PPIs is inconclusive. The present study aimed to estimate the causal effect of PPIs on the risk of dementia by target trial emulation and time-varying exposure modeling. METHODS: Using claims data of 2,698,176 insured people of a large German statutory health insurer, a target trial was conceptualized in which individuals aged 40 years and older were classified as PPI initiators or non-initiators between 2008 and 2018, and were followed until diagnosis of dementia, death, loss to follow-up or end of study. Incidence of dementia (International Classification of Diseases 10 codes F00, F01, F03, F05.1, G30, G31.0, G31.1, G31.9 and F02.8+G31.82) was defined applying a 1-year lag window. Weighted Cox models were used to estimate the effect of PPI initiation versus non-initiation on dementia risk and weighted pooled logistic regression was used to estimate the effect of time-varying use versus non-use. RESULTS: In all, 29,746 PPI initiators (4.4%) and 26,830 non-initiators (1.3%) were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio for dementia was 1.54 (95% confidence interval 1.51-1.58). The hazard ratio for time-dependent PPI use versus non-use was 1.56 (95% confidence interval 1.50-1.63). Differentiated subtypes, including unspecified dementia, Alzheimer's disease and vascular dementia, showed increased risk by PPI initiation and time-varying PPI use. CONCLUSIONS: This study suggests that PPI initiation and time-varying PPI use may increase overall dementia risk.
Subject(s)
Alzheimer Disease , Dementia , Adult , Alzheimer Disease/chemically induced , Alzheimer Disease/epidemiology , Dementia/chemically induced , Dementia/diagnosis , Dementia/epidemiology , Humans , Middle Aged , Proportional Hazards Models , Proton Pump Inhibitors/adverse effects , Risk FactorsABSTRACT
PURPOSE: The German annual drug prescription-report has indicated overuse of proton pump inhibitors (PPIs) for many years; however, little was known about the characteristics of people using PPIs. This study aimed to provide comprehensive utilization data and describe frequencies of potential on- and off-label PPI-indications in Bavaria, Germany. METHODS: Claims data of statutorily insured people from 2010 to 2018 were used. Defined daily doses (DDDs) of PPIs by type of drug, prevalence of PPI-use and DDDs prescribed per 1000 insured people/day were analyzed. For 2018, proportions of users and DDDs per 1000 insured people were calculated by age and sex. To elucidate changes in prescribing practices due to a suspected drug-drug interaction, we examined co-prescribing of clopidogrel and PPIs between 2010 and 2018. For PPI new users, sums of DDDs and frequencies of potential indications were examined. RESULTS: PPI prescribing increased linearly from 2010 to 2016 and gradually decreased from 2016 to 2018. In 2018, 14.7% of women and 12.2% of men received at least one prescription, and 64.8 DDDs (WHO-def.) per 1000 insured people/day were prescribed. Overall, omeprazole use decreased over the observation period and was steadily replaced by pantoprazole, especially when co-prescibed with clopidogrel. An on-label PPI-indication was not reported at first intake in 52.0% of new users. CONCLUSIONS: The utilization of prescribed PPIs has decreased since 2016. However, a large proportion of new PPI-users had no documentation of a potential indication, and the sums of DDDs prescribed often seemed not to comply with guidelines.
Subject(s)
Drug Utilization , Proton Pump Inhibitors , Drug Prescriptions , Female , Humans , Male , Omeprazole/therapeutic use , Practice Patterns, Physicians' , Proton Pump Inhibitors/therapeutic use , World Health OrganizationABSTRACT
AIM: Higher educational attainment is associated with a lower risk of periodontitis, but the extent to which this association is causal and mediated by intermediate factors is unclear. MATERIALS AND METHODS: Using summary data from genetic association studies from up to 1.1 million participants of European descent, univariable and multivariable Mendelian randomization analyses were performed to infer the total effect of educational attainment on periodontitis and to estimate the degree to which income, smoking, alcohol consumption, and body mass index mediate the association. RESULTS: The odds ratio of periodontitis per 1 standard deviation increment in genetically predicted education was 0.78 (95% CI: 0.68-0.89). The proportions mediated of the total effect of genetically predicted education on periodontitis were 64%, 35%, 15%, and 46% for income, smoking, alcohol consumption, and body mass index, respectively. CONCLUSIONS: Using a genetic instrumental variable approach, this study triangulated evidence from existing observational epidemiological studies and suggested that higher educational attainment lowers periodontitis risk. Measures to reduce the burden of educational disparities in periodontitis risk may tackle downstream risk factors, particularly income, smoking, and obesity.
Subject(s)
Mendelian Randomization Analysis , Periodontitis , Educational Status , Genome-Wide Association Study , Humans , Periodontitis/epidemiology , Periodontitis/genetics , Polymorphism, Single NucleotideABSTRACT
AIM: This study aimed to leverage human genetic data to investigate whether cannabis use causally affects periodontitis. MATERIALS AND METHODS: Data were obtained from summary statistics of genome-wide association studies of lifetime cannabis use (N = 184,765), cannabis use disorder (17,068 cases; 357,219 controls), and periodontitis (17,353 cases; 28,210 controls). We performed two-sample Mendelian randomization (MR) analysis using 6 genetic variants as instrumental variables for lifetime cannabis use and 11 variants as instruments for cannabis use disorder to estimate associations with periodontitis. RESULTS: There was no evidence for an association between genetic liability for lifetime cannabis use or cannabis use disorder with periodontitis. The estimates from the primary analyses were supported in multivariable MR analysis, which considered potential pleiotropic pathways and in weak instrument analyses. CONCLUSIONS: This study provides little evidence to support a detrimental effect of genetic liability for cannabis use on periodontal health.
Subject(s)
Cannabis , Marijuana Abuse , Periodontitis , Cannabis/genetics , Genome-Wide Association Study , Humans , Mendelian Randomization Analysis , Periodontitis/genetics , Polymorphism, Single NucleotideABSTRACT
AIM: Observational research suggests that periodontitis affects psoriasis. However, observational studies are prone to reverse causation and confounding, which hampers drawing causal conclusions and the effect direction. We applied the Mendelian randomization (MR) method to comprehensively assess the potential bi-directional association between periodontitis and psoriasis. MATERIALS AND METHODS: We used genetic instruments from the largest available genome-wide association study of European descent for periodontitis (17,353 cases, 28,210 controls) to investigate the relationship with psoriasis (13,229 cases, 21,543 controls), and vice versa. Causal Analysis Using Summary Effect (CAUSE) estimates and inverse variance-weighted (IVW) MR analyses were used for the primary analysis. Robust MR approaches were used for sensitivity analyses. RESULTS: Both univariable methods, CAUSE and IVW MR analyses, did not reveal any impact of periodontitis on psoriasis (CAUSE odds ratio [OR] = 1.00, p = 1.00; IVW OR = 1.02, p = .6247), or vice versa (CAUSE OR = 1.01, p = .5135; IVW OR = 1.00, p = .7070). The null association was corroborated by pleiotropy-robust methods with ORs close to 1 and p-values >.59. Overall, MR analyses did not suggest any effect of periodontitis on psoriasis. Similarly, there was no evidence to support an effect of psoriasis on periodontitis. CONCLUSIONS: Within the limitations of this MR study, the outcomes supported neither periodontitis affecting psoriasis nor psoriasis affecting periodontitis.
Subject(s)
Periodontitis , Psoriasis , Genome-Wide Association Study/methods , Humans , Mendelian Randomization Analysis/methods , Periodontitis/complications , Periodontitis/genetics , Polymorphism, Single Nucleotide , Psoriasis/complications , Psoriasis/geneticsABSTRACT
AIM: To examine the associations between bone turnover markers and periodontitis in two cross-sectional population-based studies. MATERIALS AND METHODS: We used data from two independent adult samples (N = 4993), collected within the Study of Health in Pomerania project, to analyse cross-sectional associations of N-procollagen type 1 amino-terminal propeptide (P1NP), C-terminal cross-linking telopeptide, osteocalcin, bone-specific alkaline phosphatase (BAP), fibroblast growth factor 23, wingless-type mouse mammary tumour virus integration site family member 5a (WNT5A), and sclerostin values with periodontitis. Confounder-adjusted gamma and fractional response regression models were applied. RESULTS: Positive associations were found for P1NP with mean pocket probing depth (PPD; eß=1.008 ; 95% confidence interval [CI]: 1.001-1.015), mean clinical attachment loss (mean CAL; eß=1.027 ; 95% CI: 1.011-1.044), and proportion of sites with bleeding on probing (%BOP; eß=1.055 ; 95% CI: 1.005-1.109). Similar associations were seen for BAP with %BOP ( eß=1.121 ; 95% CI: 1.042-1.205), proportion of sites with PPD ≥4 mm (%PPD4) ( eß=1.080 ; 95% CI: 1.005-1.161), and sclerostin with %BOP ( eß=1.308 ; 95% CI: 1.005-1.704). WNT5A was inversely associated with mean PPD ( eß=0.956 ; 95% CI: 0.920-0.993) and %PPD4 ( eß=0.794 ; 95% CI: 0.642-0.982). CONCLUSIONS: This study revealed scattered associations of P1NP, BAP, WNT5A, and sclerostin with periodontitis, but the results are contradictory in the overall context. Associations reported in previous studies could not be confirmed.
Subject(s)
Bone Remodeling , Periodontitis , Alkaline Phosphatase , Animals , Biomarkers , Bone Remodeling/physiology , Collagen Type I , Cross-Sectional Studies , MiceABSTRACT
BACKGROUND: Physical activity has been positively related to malignant melanoma. However, that association may be confounded by ultraviolet radiation (UV), a variable closely related to both outdoor physical activity and malignant melanoma. We examined physical activity, grip strength and sedentary behaviour in relation to risk of malignant melanoma, accounting for relevant confounders using data from a prospective cohort study. METHODS: In 350,512 UK Biobank participants aged 38-73 years at baseline, physical activity was assessed with a modified version of the International Physical Activity Questionnaire Short Form, grip strength was measured with a hand dynamometer, and sedentary behaviour was recorded with three specific questions. Multivariable hazard ratios (HR) and corresponding 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. RESULTS: During 7 years of follow-up, 1239 incident malignant melanoma diagnoses were recorded. Physical activity and sedentary behaviour were unrelated to malignant melanoma (HRs 1.01 (95% CI 0.95-1.07) and 1.04 (95% CI 0.97-1.12), respectively), and the initially positive association with grip strength in the basic model (HR 1.23, 95% CI 1.08-1.40) was attenuated after full adjustment (HR 1.10, 95% CI 0.96-1.26). CONCLUSION: Physical activity, grip strength and sedentary behaviour are not associated with malignant melanoma risk.
Subject(s)
Exercise/statistics & numerical data , Hand Strength/physiology , Melanoma/epidemiology , Adult , Aged , Biological Specimen Banks , Female , Humans , Incidence , Male , Melanoma/etiology , Middle Aged , Prospective Studies , Risk Factors , Sedentary Behavior , United Kingdom/epidemiologyABSTRACT
OBJECTIVE: Identifying potentially modifiable risk factors for ovarian cancer is essential for prevention because this cancer is predominantly detected at a late stage. Here, we estimated the relations of general adiposity and measures reflecting body fat distribution to the risk of epithelial ovarian cancer. METHODS: We ascertained 683 ovarian epithelial cancers (343 high-grade serous, 141 non-high grade serous) among 145,575 women, aged 50-72 years (median follow-up 12.6 years), from the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study. Using Cox models, we estimated confounder-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for associations of overall ovarian cancer, high-grade serous and non-high-grade serous carcinoma with body mass index, waist circumference, hip circumference, waist-hip ratio, waist-height ratio, body adiposity index, body shape index, and abdominal volume index. RESULTS: Anthropometric measures were unrelated to overall ovarian cancer, high-grade serous cancer, and non-high-grade serous cancer. For example, the HR for overall ovarian cancer per standard deviation increment of body mass index at baseline was 0.98 (95% CI 0.88-1.10). Similar associations were observed with measurements of body fat distribution. CONCLUSION: These results do not indicate that adult adiposity is associated with ovarian cancer risk in post-menopausal women.