scholarly journals Smoking methylation marks for prediction of urothelial cancer risk

2021 ◽  
Author(s):  
Chenglong Yu ◽  
Kristina M. Jordahl ◽  
Julie K. Bassett ◽  
Jihoon Eric Joo ◽  
Ee Ming Wong ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Risk Prediction ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Conditional Logistic Regression ◽  
Area Under The Curve ◽  
Testing Dataset ◽  
Smoking Exposure ◽  
Melbourne Collaborative Cohort Study ◽  
Confounder Adjustment

AbstractBackgroundSelf-reported information may not accurately capture smoking exposure. We aimed to evaluate whether smoking-associated DNA methylation markers improve urothelial cell carcinoma (UCC) risk prediction.MethodsConditional logistic regression was used to assess associations between blood-based methylation and UCC risk using two matched case-control samples, N=404 pairs from the Melbourne Collaborative Cohort Study (MCCS) and N=440 pairs from the Women’s Health Initiative (WHI) cohort, respectively. Results were pooled using fixed-effects meta-analysis. We developed methylation-based predictors of UCC and evaluated their prediction accuracy on two replication datasets using the area under the curve (AUC).ResultsThe meta-analysis identified associations (P<4.7×10−5) for 29 of 1,061 smoking-associated methylation sites, but these were substantially attenuated after adjustment for self-reported smoking. Nominally significant associations (P<0.05) were found for 387 (36%) and 86 (8%) of smoking-associated markers without/with adjustment for self-reported smoking, respectively, with same direction of association as with smoking for 387 (100%) and 79 (92%) markers. A Lasso-based predictor was associated with UCC risk in one replication dataset in MCCS (N=134, odds ratio per SD [OR]=1.37, 95%CI=1.00-1.90) after confounder adjustment; AUC=0.66, compared with AUC=0.64 without methylation information. Limited evidence of replication was found in the second testing dataset in WHI (N=440, OR=1.09, 95%CI=0.91-1.30).ConclusionsCombination of smoking-associated methylation marks may provide some improvement to UCC risk prediction. Our findings need further evaluation using larger datasets.ImpactDNA methylation may be associated with UCC risk beyond traditional smoking assessment and could contribute to some improvements in stratification of UCC risk in the general population.

scholarly journals Risk Factors Associated with Irreversible Airway Obstruction in Asthma: A Systematic Review and Meta-Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Lanlan Zhang ◽  
Lixiu He ◽  
Jin Gong ◽  
Chuntao Liu
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Atopic Dermatitis ◽  
Airway Obstruction ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Case Control Studies ◽  
Smoking Exposure ◽  
Asthma Patients ◽  
Irreversible Airway Obstruction

Irreversible airway obstruction (IAO) is a subtype of asthma and relates to poorer prognosis in some asthma patients. However, the prevalence and risk factors for IAO are unknown. A systematic review regarding controlled clinical studies (cohort, case-control studies) on IAO asthma in adult and/or children affected by asthma/early wheeze was performed. Eighteen papers were identified in this study. It was reported that the incidence of IAO at random effects or fixed effects in severe asthma and nonsevere asthma was 0.54 (95% CI: 0.45–0.62) and 0.16 (95% CI: 0.12–0.20), respectively. In IAO asthma, the pooled odds ratio (OR) related to smoking exposure was 2.22 (95% CI: 1.82–2.73), the OR for male, smoking, and fractional exhaled nitric oxide (FENO) was 2.22 (95% CI: 1.82–2.7), 1.79 (95% CI: 1.46–2.19), and 2.16 (95% CI: 1.05–4.43), respectively, suggesting these factors increase the risk of IAO. However, a decreased OR in IAO asthma was observed due to rhinitis (OR = 0.31, 95% CI: 0.24–0.40), atopy (OR = 0.584, 95% CI: 0.466–0.732), and atopic dermatitis (OR = 0.60, 95% CI: 0.42–0.85), indicating these factors are associated with reduced risk of IAO. IAO in asthma is associated with gender, smoking, FENO, rhinitis, atopy, and atopic dermatitis.

scholarly journals DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Eilis Hannon ◽  
Emma L Dempster ◽  
Georgina Mansell ◽  
Joe Burrage ◽  
Nick Bass ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Association Studies ◽  
Meta Analysis ◽  
Genetic Association Studies ◽  
Methylation Data ◽  
Treatment Resistant ◽  
Systematic Analysis ◽  
Factors Associated ◽  
Cell Counts ◽  
Smoking Exposure

We performed a systematic analysis of blood DNA methylation profiles from 4,483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1,048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia.

scholarly journals DNA methylation biomarkers of myocardial infarction and cardiovascular disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Alba Fernández-Sanlés ◽  
Sergi Sayols-Baixeras ◽  
Isaac Subirana ◽  
Mariano Sentí ◽  
S. Pérez-Fernández ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Dna Methylation ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Risk Function ◽  
Risk Scores ◽  
Clinical Value ◽  
Predictive Capacity ◽  
Two Samples

Abstract Background The epigenetic landscape underlying cardiovascular disease (CVD) is not completely understood and the clinical value of the identified biomarkers is still limited. We aimed to identify differentially methylated loci associated with acute myocardial infarction (AMI) and assess their validity as predictive and causal biomarkers. Results We designed a case–control, two-stage, epigenome-wide association study on AMI (ndiscovery = 391, nvalidation = 204). DNA methylation was assessed using the Infinium MethylationEPIC BeadChip. We performed a fixed-effects meta-analysis of the two samples. 34 CpGs were associated with AMI. Only 12 of them were available in two independent cohort studies (n ~ 1800 and n ~ 2500) with incident coronary and cardiovascular disease (CHD and CVD, respectively). The Infinium HumanMethylation450 BeadChip was used in those two studies. Four of the 12 CpGs were validated in association with incident CHD: AHRR-mapping cg05575921, PTCD2-mapping cg25769469, intergenic cg21566642 and MPO-mapping cg04988978. We then assessed whether methylation risk scores based on those CpGs improved the predictive capacity of the Framingham risk function, but they did not. Finally, we aimed to study the causality of those associations using a Mendelian randomization approach but only one of the CpGs had a genetic influence and therefore the results were not conclusive. Conclusions We have identified 34 CpGs related to AMI. These loci highlight the relevance of smoking, lipid metabolism, and inflammation in the biological mechanisms related to AMI. Four were additionally associated with incident CHD and CVD but did not provide additional predictive information.

scholarly journals DNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis

Blood ◽  
2018 ◽  
Vol 132 (17) ◽  
pp. 1842-1850 ◽  
Author(s):  
Cavin K. Ward-Caviness ◽  
Jennifer E. Huffman ◽  
Karl Everett ◽  
Marine Germain ◽  
Jenny van Dongen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Confidence Interval ◽  
Fixed Effects ◽  
Meta Analysis ◽  
African Ancestry ◽  
Clotting Time ◽  
Age Related ◽  
Epigenetic Aging ◽  
Hemostatic Factors ◽  
Pai 1

Abstract Many hemostatic factors are associated with age and age-related diseases; however, much remains unknown about the biological mechanisms linking aging and hemostatic factors. DNA methylation is a novel means by which to assess epigenetic aging, which is a measure of age and the aging processes as determined by altered epigenetic states. We used a meta-analysis approach to examine the association between measures of epigenetic aging and hemostatic factors, as well as a clotting time measure. For fibrinogen, we performed European and African ancestry–specific meta-analyses which were then combined via a random effects meta-analysis. For all other measures we could not estimate ancestry-specific effects and used a single fixed effects meta-analysis. We found that 1-year higher extrinsic epigenetic age as compared with chronological age was associated with higher fibrinogen (0.004 g/L/y; 95% confidence interval, 0.001-0.007; P = .01) and plasminogen activator inhibitor 1 (PAI-1; 0.13 U/mL/y; 95% confidence interval, 0.07-0.20; P = 6.6 × 10−5) concentrations, as well as lower activated partial thromboplastin time, a measure of clotting time. We replicated PAI-1 associations using an independent cohort. To further elucidate potential functional mechanisms, we associated epigenetic aging with expression levels of the PAI-1 protein encoding gene (SERPINE1) and the 3 fibrinogen subunit-encoding genes (FGA, FGG, and FGB) in both peripheral blood and aorta intima-media samples. We observed associations between accelerated epigenetic aging and transcription of FGG in both tissues. Collectively, our results indicate that accelerated epigenetic aging is associated with a procoagulation hemostatic profile, and that epigenetic aging may regulate hemostasis in part via gene transcription.

scholarly journals DNA Methylation Biomarkers Of Myocardial Infarction And Cardiovascular Disease

2019 ◽  
Author(s):  
Alba Fernández-Sanlés ◽  
Sergi Sayols-Baixeras ◽  
Isaac Subirana ◽  
Mariano Sentí ◽  
S Pérez-Fernández ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Acute Myocardial Infarction ◽  
Dna Methylation ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Risk Function ◽  
Added Value ◽  
Predictive Capacity ◽  
Exposure Variable

ABSTRACTObjectiveTo assess the association between DNA methylation and acute myocardial infarction, the predictive added value of the identified methylation marks, and the causality of those associations.Approach and ResultsWe conducted a case-control, two-stage, epigenome-wide association study on acute myocardial infarction (ndiscovery=391, nvalidation=204). DNA methylation was assessed using the Infinium MethylationEPIC BeadChip (over 850,000 CpGs). DNA methylation was the exposure variable and myocardial infarction the outcome of interest. After a fixed-effects meta-analysis, 34 CpGs fulfilled Bonferroni significance. These findings were also analysed in two independent cohort studies (n∼1,800 and n∼2,500) with incident coronary (CHD) and cardiovascular disease (CVD). The Infinium HumanMethylation450 BeadChip was used in these two studies (over 480,000 CpGs) and only 12 of the 34 CpGs were available in those samples. Finally, we validated four of them in association with incident CHD: AHRR-mapping cg05575921, PTCD2-mapping cg25769469, intergenic cg21566642 and MPO-mapping cg04988978. The four CpGs were also associated with classical cardiovascular risk factors. A methylation risk score based on those CpGs did not improve the predictive capacity of the Framingham risk function. To assess the causal effects of those CpGs we performed Mendelian randomization analysis but only one metQTL could be identified and the results were not conclusive.ConclusionsWe have identified 34 CpGs related to acute myocardial infarction. These loci highlight the relevance of smoking, lipid metabolism, and inflammation in the biological mechanisms related to myocardial infarction. Four were additionally associated with incident CHD and CVD but did not provide additional predictive information.

A Systematic Review and Meta-Analysis about the Effect of Bisphosphonates on the Risk of Skeletal-Related Event in Men with Prostate Cancer

2020 ◽  
Vol 20 (13) ◽  
pp. 1604-1612
Author(s):  
Congcong Wu ◽  
Hua Jiang ◽  
Jianghua Chen
Keyword(s):  
Prostate Cancer ◽  
Fixed Effects ◽  
Data Extraction ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Control Group ◽  
Fixed Effects Model ◽  
Related Event ◽  
Mineral Density ◽  
Skeletal Related Event

Background: Although the adjuvant therapy of bisphosphonates in prostate cancer is effective in improving bone mineral density, it is still uncertain whether bisphosphonates could decrease the risk of Skeletal- Related Event (SRE) in patients with prostate cancer. We reviewed and analyzed the effect of different types of bisphosphonates on the risk of SRE, defined as pathological fracture, spinal cord compression, radiation therapy to the bone, surgery to bone, hypercalcemia, bone pain, or death as a result of prostate cancer. Methods: A systemic literature search was conducted on PubMed and related bibliographies. The emphasis during data extraction was laid on the Hazard Ratio (HR) and the corresponding 95% Confidence Interval (CI) from every eligible Randomized Controlled Trial (RCT). HR was pooled with the fixed effects model, and preplanned subgroup analyses were performed. Results: 5 RCTs (n = 4651) were included and analyzed finally after screening 51 articles. The meta-analysis of all participants showed no significant decrease in the risk of SRE when adding bisphosphonates to control group (HR = 0.968, 95% CI = 0.874 - 1.072, p = 0.536) with low heterogeneity (I2 = 0.0% (d.f. = 4) p = 0.679). There was no significant improvement on SRE neither in the subgroups with Metastases (M1) or Castration-Sensitive Prostate Cancer (CSPC) (respectively HR = 0.968, 95% CI = 0.874 - 1.072, p = 0.536, I2 = 0.0% (d.f. = 4) p = 0.679; HR = 0.954, 95% CI = 0.837 - 1.088, p = 0.484, I2 = 0.0% (d.f. = 3) p = 0.534). Conclusion: Our study demonstrated that bisphosphonates could not statistically significantly reduce the risk of SRE in patients with prostate cancer, neither in the subgroups with M1 or CSPC.

scholarly journals Profile of copper-associated DNA methylation and its association with incident acute coronary syndrome

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Pinpin Long ◽  
Qiuhong Wang ◽  
Yizhi Zhang ◽  
Xiaoyan Zhu ◽  
Kuai Yu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Acute Coronary Syndrome ◽  
Methylation Level ◽  
Meta Analysis ◽  
Regulation Of Gene Expression ◽  
Density Lipoprotein ◽  
Blood Leukocytes ◽  
Coronary Syndrome ◽  
A Genome ◽  
Increased Risk

Abstract Background Acute coronary syndrome (ACS) is a cardiac emergency with high mortality. Exposure to high copper (Cu) concentration has been linked to ACS. However, whether DNA methylation contributes to the association between Cu and ACS is unclear. Methods We measured methylation level at > 485,000 cytosine-phosphoguanine sites (CpGs) of blood leukocytes using Human Methylation 450 Bead Chip and conducted a genome-wide meta-analysis of plasma Cu in a total of 1243 Chinese individuals. For plasma Cu-related CpGs, we evaluated their associations with the expression of nearby genes as well as major cardiovascular risk factors. Furthermore, we examined their longitudinal associations with incident ACS in the nested case-control study. Results We identified four novel Cu-associated CpGs (cg20995564, cg18608055, cg26470501 and cg05825244) within a 5% false discovery rate (FDR). DNA methylation level of cg18608055, cg26470501, and cg05825244 also showed significant correlations with expressions of SBNO2, BCL3, and EBF4 gene, respectively. Higher DNA methylation level at cg05825244 locus was associated with lower high-density lipoprotein cholesterol level and higher C-reactive protein level. Furthermore, we demonstrated that higher cg05825244 methylation level was associated with increased risk of ACS (odds ratio [OR], 1.23; 95% CI 1.02–1.48; P = 0.03). Conclusions We identified novel DNA methylation alterations associated with plasma Cu in Chinese populations and linked these loci to risk of ACS, providing new insights into the regulation of gene expression by Cu-related DNA methylation and suggesting a role for DNA methylation in the association between copper and ACS.

scholarly journals The Potential Diagnostic Accuracy of Circulating MicroRNAs for Leukemia: A Meta-Analysis

2021 ◽  
Vol 20 ◽  
pp. 153303382110119
Author(s):  
Wen-Ting Zhang ◽  
Guo-Xun Zhang ◽  
Shuai-Shuai Gao
Keyword(s):  
Diagnostic Accuracy ◽  
Likelihood Ratio ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Diagnostic Odds Ratio ◽  
Circulating Micrornas ◽  
Sensitivity Specificity

Background: Leukemia is a common malignant disease in the human blood system. Many researchers have proposed circulating microRNAs as biomarkers for the diagnosis of leukemia. We conducted a meta-analysis to evaluate the diagnostic accuracy of circulating miRNAs in the diagnosis of leukemia. Methods: A comprehensive literature search (updated to October 13, 2020) in PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang database and China National Knowledge Infrastructure (CNKI) was performed to identify eligible studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) for diagnosing leukemia were pooled for both overall and subgroup analysis. The meta-regression and subgroup analysis were performed to explore heterogeneity and Deeks’ funnel plot was used to assess publication bias. Results: 49 studies from 22 publications with a total of 3,489 leukemia patients and 2,756 healthy controls were included in this meta-analysis. The overall sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the curve were 0.83, 0.92, 10.8, 0.18, 59 and 0.94, respectively. Subgroup analysis shows that the microRNA clusters of plasma type could carry out a better diagnostic accuracy of leukemia patients. In addition, publication bias was not found. Conclusions: Circulating microRNAs can be used as a promising noninvasive biomarker in the early diagnosis of leukemia.

scholarly journals Effect of interventions based on educational technologies on the prevention of sexually transmitted infections in incarcerated women: protocol of a systematic review and meta-analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. e043373
Author(s):  
Isaiane da Silva Carvalho ◽  
Ryanne Carolynne Marques Gomes Mendes ◽  
Priscila de Oliveira Cabral Melo ◽  
Caroline Ferraz Simões ◽  
Luciana Pedrosa Leal ◽  
...  
Keyword(s):  
Systematic Review ◽  
Health Education ◽  
Sexually Transmitted Infections ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Incarcerated Women ◽  
Mean Difference ◽  
World Health ◽  
Educational Technologies ◽  
Sexually Transmitted

IntroductionPrisons are places with high vulnerability and high risk for the development of sexually transmitted infections. World Health Agencies recommend establishing intervention measures, such as information and education, on the prevention of diseases. Thus, technologies as tools for health education have been used to reduce sexually transmitted infections. However, no systematic review has investigated the effectiveness of these interventions. Therefore, this review’s objective is to examine the effect of educational technologies used for preventing sexually transmitted infections in incarcerated women.Methods and analysisPreferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be strictly followed. The following electronic databases will be searched: Scopus; Cumulative Index of Nursing and Allied Health, Education Resources Information Center, Embase, PsycINFO, PubMed/Medline, Web of Science and Google Scholar. Randomised clinical trials of interventions that used educational technologies to prevent sexually transmitted infections in incarcerated women will be searched in the databases from the beginning of 2020 until December by two researchers independently. A narrative synthesis will be constructed for all included studies, and if there are sufficient data, a meta-analysis will be performed using the Review Manager software (V.5.3). Continuous results will be presented as the weighted mean difference or the standardised mean difference with 95% CIs. Under the heterogeneity of the included studies, a random-effects or fixed-effects model will be used. The studies’ heterogeneity will be assessed by the I2 method. The sensitivity analysis will be carried out to examine the magnitude of each study’s influence on the general results. A significance level of p≤0.05 will be adopted.Ethics and disclosureEthical approval is not required because no primary data will be collected. The results will be published in journals reviewed by peers.PROSPERO registration numberCRD42020163820.

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