scholarly journals Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group

2019 ◽  
Author(s):  
Tianye Jia ◽  
Congying Chu ◽  
Yun Liu ◽  
Jenny van Dongen ◽  
Evangelos Papastergios ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Nucleus Accumbens ◽  
Large Scale ◽  
Biomarker Discovery ◽  
Association Studies ◽  
Meta Analysis ◽  
Hippocampal Volume ◽  
Small Sample ◽  
Small Sample Sizes ◽  
Meta Analyses

AbstractDNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)—three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.

scholarly journals Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group

2018 ◽  
Author(s):  
Tianye Jia ◽  
Congying Chu ◽  
Yun Liu ◽  
Jenny van Dongen ◽  
Nicola J Armstrong ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cell ◽  
Nucleus Accumbens ◽  
Cell Fate ◽  
Large Scale ◽  
Biomarker Discovery ◽  
Association Studies ◽  
Regulatory Elements ◽  
Hippocampal Volume ◽  
Small Sample

ABSTRACTDNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3,337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc) –three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. CpG sites associated with hippocampus volume were significantly enriched within cancer-related genes and within regulatory elements containing the transcriptionally repressive histone H3K27 tri-methylation mark that is vital for stem cell fate specification. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.

Clinical outcomes of cancer patients with COVID-19: A systematic review and meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18600-e18600
Author(s):  
Maryam Alasfour ◽  
Salman Alawadi ◽  
Malak AlMojel ◽  
Philippos Apolinario Costa ◽  
Priscila Barreto Coelho ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Meta Analysis ◽  
Small Sample ◽  
Prediction Intervals ◽  
Invasive Ventilation ◽  
Newcastle Ottawa Scale ◽  
Small Sample Sizes ◽  
Meta Analyses

e18600 Background: Patients with coronavirus disease 2019 (COVID-19) and cancer have worse clinical outcomes compared to those without cancer. Primary studies have examined this population, but most had small sample sizes and conflicting results. Prior meta-analyses exclude most US and European data or only examine mortality. The present meta-analysis evaluates the prevalence of several clinical outcomes in cancer patients with COVID-19, including new emerging data from Europe and the US. Methods: A systematic search of PubMED, medRxiv, JMIR and Embase by two independent investigators included peer-reviewed papers and preprints up to July 8, 2020. The primary outcome was mortality. Other outcomes were ICU and non-ICU admission, mild, moderate and severe complications, ARDS, invasive ventilation, stable, and clinically improved rates. Study quality was assessed through the Newcastle–Ottawa scale. Random effects model was used to derive prevalence rates, their 95% confidence intervals (CI) and 95% prediction intervals (PI). Results: Thirty-four studies (N = 4,371) were included in the analysis. The mortality prevalence rate was 25.2% (95% CI: 21.1–29.7; 95% PI: 9.8-51.1; I 2 = 85.4), with 11.9% ICU admissions (95% CI: 9.2-15.4; 95% PI: 4.3-28.9; I 2= 77.8) and 25.2% clinically stable (95% CI: 21.1-29.7; 95% PI: 9.8-51.1; I 2 = 85.4). Furthermore, 42.5% developed severe complications (95% CI: 30.4-55.7; 95% PI: 8.2-85.9; I 2 = 94.3), with 22.7% developing ARDS (95% CI: 15.4-32.2; 95% PI: 5.8-58.6; I 2 = 82.4), and 11.3% needing invasive ventilation (95% CI: 6.7-18.4; 95% PI: 2.3-41.1; I 2 = 79.8). Post-follow up, 49% clinically improved (95% CI: 35.6-62.6; 95% PI: 9.8-89.4; I 2 = 92.5). All outcomes had large I 2 , suggesting high levels of heterogeneity among studies, and wide PIs indicating high variability within outcomes. Despite this variability, the mortality rate in cancer patients with COVID-19, even at the lower end of the PI (9.8%), is higher than the 2% mortality rate of the non-cancer with COVID-19 population, but not as high as what other meta-analyses conclude, which is around 25%. Conclusions: Patients with cancer who develop COVID-19 have a higher probability of mortality compared to the general population with COVID-19, but possibly not as high as previous studies have shown. A large proportion of them developed severe complications, but a larger proportion recovered. Prevalence of mortality and other outcomes published in prior meta-analyses did not report prediction intervals, which compromises the clinical utilization of such results.

Abstract P260: Large-scale Meta-analysis of Diverse Ancestry Genome-wide Association Studies to Identify Pharmacogenomic Interactions of Sulfonylureas and ECG Phenotypes

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
James S Floyd ◽  
Colleen Sitlani ◽  
Christy L Avery ◽  
Eric A Whitsel ◽  
Leslie Lange ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Qt Interval ◽  
Association Studies ◽  
Meta Analysis ◽  
Small Sample ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Meta Analyses

Introduction: Sulfonylureas are a commonly-used class of diabetes medication that can prolong the QT-interval, which is a leading cause of drug withdrawals from the market given the possible risk of life-threatening arrhythmias. Previously, we conducted a meta-analysis of genome-wide association studies of sulfonylurea-genetic interactions on QT interval among 9 European-ancestry (EA) cohorts using cross-sectional data, with null results. To improve our power to identify novel drug-gene interactions, we have included repeated measures of medication use and QT interval and expanded our study to include several additional cohorts, including African-American (AA) and Hispanic-ancestry (HA) cohorts with a high prevalence of sulfonylurea use. To identify potentially differential effects on cardiac depolarization and repolarization, we have also added two phenotypes - the JT and QRS intervals, which together comprise the QT interval. Hypothesis: The use of repeated measures and expansion of our meta-analysis to include diverse ancestry populations will allow us to identify novel pharmacogenomic interactions for sulfonylureas on the ECG phenotypes QT, JT, and QRS. Methods: Cohorts with unrelated individuals used generalized estimating equations to estimate interactions; cohorts with related individuals used mixed effect models clustered on family. For each ECG phenotype (QT, JT, QRS), we conducted ancestry-specific (EA, AA, HA) inverse variance weighted meta-analyses using standard errors based on the t-distribution to correct for small sample inflation in the test statistic. Ancestry-specific summary estimates were combined using MANTRA, an analytic method that accounts for differences in local linkage disequilibrium between ethnic groups. Results: Our study included 65,997 participants from 21 cohorts, including 4,020 (6%) sulfonylurea users, a substantial increase from the 26,986 participants and 846 sulfonylureas users in the previous meta-analysis. Preliminary ancestry-specific meta-analyses have identified genome-wide significant associations (P < 5х10–8) for each ECG phenotype, and analyses with MANTRA are in progress. Conclusions: In the setting of the largest collection of pharmacogenomic studies to date, we used repeated measurements and leveraged diverse ancestry populations to identify new pharmacogenomic loci for ECG traits associated with cardiovascular risk.

Effectiveness of Outdoor Exercise Parks on Health Outcomes in Older Adults—A Mixed-Methods Systematic Review and Meta-Analysis

2020 ◽  
pp. 1-13
Author(s):  
Yoke Leng Ng ◽  
Keith D. Hill ◽  
Pazit Levinger ◽  
Elissa Burton
Keyword(s):  
Physical Activity ◽  
Systematic Review ◽  
Older Adults ◽  
Meta Analysis ◽  
Small Sample ◽  
Activity Levels ◽  
Single Leg Stance ◽  
Small Sample Sizes ◽  
Meta Analyses

The objective of this systematic review was to examine the effectiveness of outdoor exercise park equipment on physical activity levels, physical function, psychosocial outcomes, and quality of life of older adults living in the community and to evaluate the evidence of older adults’ use of outdoor exercise park equipment. A search strategy was conducted from seven databases. Nine articles met the inclusion criteria. The study quality results were varied. Meta-analyses were undertaken for two physical performance tests: 30-s chair stand test and single-leg stance. The meta-analysis results were not statistically significant. It was not possible to conclude whether exercise parks were effective at improving levels of physical activity. The review shows that older adults value the benefits of health and social interaction from the use of exercise parks. Findings should be interpreted with caution due to the small sample sizes and the limited number of studies.

scholarly journals Building theories of consistency and variability in children’s language development: A large-scale data approach

2021 ◽  
Author(s):  
Angeline Tsui ◽  
Virginia A. Marchman ◽  
Michael C. Frank
Keyword(s):  
Language Learning ◽  
Data Aggregation ◽  
Large Scale ◽  
Meta Analysis ◽  
Secondary Data ◽  
Small Sample ◽  
Early Language ◽  
Large Scale Data ◽  
Small Sample Sizes ◽  
Scale Data

Young children typically begin learning words during their first two years of life. On the other hand, they also vary substantially in their language learning. Similarities and differences in language learning call for a quantitative theory that can predict and explain which aspects of early language are consistent and which are variable. However, current developmental research practices limit our ability to build such quantitative theories because of small sample sizes and challenges related to reproducibility and replicability. In this chapter, we suggest that three approaches – meta-analysis, multi-site collaborations, and secondary data aggregation – can together address some of the limitations of current research in the developmental area. We review the strengths and limitations of each approach and end by discussing the potential impacts of combining these three approaches.

scholarly journals HASE: Framework for efficient high-dimensional association analyses

2016 ◽  
Author(s):  
G.V. Roshchupkin ◽  
H.H.H. Adams ◽  
M.W. Vernooij ◽  
A. Hofman ◽  
C.M. Van Duijn ◽  
...  
Keyword(s):  
Large Scale ◽  
Association Studies ◽  
Meta Analysis ◽  
High Dimensional ◽  
Total N ◽  
Association Analyses ◽  
Large Scale Data ◽  
Individual Participant ◽  
Intermediate Results ◽  
Meta Analyses

ABSTRACTLarge-scale data collection and processing have facilitated scientific discoveries in fields such as genomics and imaging, but cross-investigations between multiple big datasets remain impractical. Computational requirements of high-dimensional association studies are often too demanding for individual sites. Additionally, the sheer size of intermediate results is unfit for collaborative settings where summary statistics are exchanged for meta-analyses. Here we introduce the HASE framework to perform high-dimensional association studies with dramatic reduction in both computational burden and storage requirements of intermediate results. We implemented a novel meta-analytical method that yields identical power as pooled analyses without the need of sharing individual participant data. The efficiency of the framework is illustrated by associating 9 million genetic variants with 1.5 million brain imaging voxels in three cohorts (total N=4,034) followed by meta-analysis, on a standard computational infrastructure. These experiments indicate that HASE facilitates high-dimensional association studies enabling large multicenter association studies for future discoveries.

Jackson and Schuler (1985) Revisited: A Meta-Analysis of the Relationships Between Role Ambiguity, Role Conflict, and Job Performance

2000 ◽  
Vol 26 (1) ◽  
pp. 155-169 ◽  
Author(s):  
Travis C. Tubre ◽  
Judith M. Collins
Keyword(s):  
Job Performance ◽  
Role Conflict ◽  
Role Ambiguity ◽  
Meta Analysis ◽  
Negative Relationship ◽  
Small Sample ◽  
Reliability Estimates ◽  
And Performance ◽  
Small Sample Sizes ◽  
Meta Analyses

We conducted a meta-analysis of correlations between role ambiguity and job performance and role conflict and job performance. Previous meta-analyses of these role constructs and performance relationships (e.g., Jackson & Schuler, 1985) were limited by small sample sizes and sparse reporting of reliability estimates in primary studies. The present study used a comprehensive database with a larger sample size and a distribution of interrater reliabilities to extend the previous findings. We also tested moderator hypotheses proposed but not conducted by Jackson and Schuler. Results revealed a negative relationship (r52.21) between role ambiguity and job performance with moderating influences due to job type and rating source. A negligible relationship (r52.07) was observed for role conflict and job performance, a finding consistent across job types and rating sources. Conclusions were that role ambiguity ought not to be dismissed as an unimportant variable in the job performance domain.

scholarly journals Changing the logic of replication: A case from infant studies

2019 ◽  
Author(s):  
Francesco Margoni ◽  
Martin Shepperd
Keyword(s):  
Statistical Power ◽  
Sampling Error ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Small Sample ◽  
Infant Research ◽  
Replication Studies ◽  
Wide Range ◽  
Small Sample Sizes ◽  
Meta Analyses

Infant research is making considerable progresses. However, among infant researchers there is growing concern regarding the widespread habit of undertaking studies that have small sample sizes and employ tests with low statistical power (to detect a wide range of possible effects). For many researchers, issues of confidence may be partially resolved by relying on replications. Here, we bring further evidence that the classical logic of confirmation, according to which the result of a replication study confirms the original finding when it reaches statistical significance, could be usefully abandoned. With real examples taken from the infant literature and Monte Carlo simulations, we show that a very wide range of possible replication results would in a formal statistical sense constitute confirmation as they can be explained simply due to sampling error. Thus, often no useful conclusion can be derived from a single or small number of replication studies. We suggest that, in order to accumulate and generate new knowledge, the dichotomous view of replication as confirmatory/disconfirmatory can be replaced by an approach that emphasizes the estimation of effect sizes via meta-analysis. Moreover, we discuss possible solutions for reducing problems affecting the validity of conclusions drawn from meta-analyses in infant research.

scholarly journals Modulation of naturalistic maladaptive memories using behavioural and pharmacological reconsolidation-interfering strategies: A systematic review and meta-analysis of clinical and 'sub-clinical' studies

2018 ◽  
Author(s):  
Katie H Walsh ◽  
Ravi K Das ◽  
Michael E Saladin ◽  
Sunjeev K Kamboj
Keyword(s):  
Substance Use ◽  
Meta Analysis ◽  
Small Sample ◽  
Future Research ◽  
Pharmacological Interventions ◽  
Treatment Type ◽  
Small Sample Sizes ◽  
Meta Analyses ◽  
Use Studies ◽  
Behavioural Strategies

Consolidated memories can undergo enduring modification through retrieval-dependent treatments that modulate reconsolidation. This has been suggested to represent a potentially transformative clinical strategy for weakening or overwriting the maladaptive memories that underlie substance use and anxiety/trauma-related disorders. However, the ability to modulate naturalistic maladaptive memories may be limited by boundary conditions imposed on reconsolidation by the nature of these memories. As such, the true potential of reconsolidation therapy is currently unknown. Here, we report a meta-analyses of behavioural and pharmacological studies examining retrieval-dependent modulation of reward and threat memories in (sub)clinical substance use and anxiety/trauma respectively. Of 4936 publications assessed for eligibility, 7 studies of substance use, and 9 of anxiety (phobia) and trauma-related symptoms were included in the meta-analyses. Overall, the findings were in the predicted direction, with the majority of effect sizes favouring the Retrieval + Treatment condition. However, the magnitude of effects depended upon the nature of the treatment type, with pharmacological interventions (relative to behavioural strategies) showing a clearer beneficial effect in studies of phobia/trauma and post-retrieval behavioural strategies, a (significantly) larger effect in substance use studies. However, high levels of heterogeneity and small sample sizes limit the strength of conclusions that can be drawn at this stage of inquiry. We hope this review will provide an impetus to address these issues in future research.

scholarly journals The effectiveness of parent training for children with autism spectrum disorder: a systematic review and meta-analyses

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Shoumitro Deb ◽  
Ameeta Retzer ◽  
Meera Roy ◽  
Rupali Acharya ◽  
Bharati Limbu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Parent Training ◽  
Large Scale ◽  
Treatment Effects ◽  
Meta Analysis ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Small Sample ◽  
Control Group ◽  
Meta Analyses

Abstract Background Various parent training interventions have been shown to have some effect on the symptoms of children with autism. We carried out a systematic review and meta-analyses to assess effectiveness of parental training for children with autism on their symptoms and parental stress. Methods Four electronic databases, CINAHL, EMBASE, MEDLINE and PsycINFO were searched until March 2020 for relevant literature. Two reviewers independently screened bibliographies using an eligibility checklist and extracted data using a structured proforma. We have also carried out meta-analyses when data were available for pooling. Results Seventeen papers from 15 studies were included for data analysis. Fifteen papers showed a positive treatment effect when compared with the control group, although not always significant. Meta-analysis based on pooled data from only two studies in each respective intervention, showed small to moderate treatment effects for three interventions, DIR/Floortime, Pivotal Response and Parent focused training respectively. Conclusions As in previous systematic reviews there was a mild to moderate treatment effects of three specific types of interventions respectively. However, it was difficult to draw any definitive conclusion about the effectiveness and generalisability of any intervention because of the wide variation in the interventions, control groups, outcome measures, small sample size, small number of studies in meta-analysis, overlap between the intervention and control procedures used in the included studies. There is an urgent need for experts in various international centres to jointly standardise a parent training intervention for children with autism and carry out a large scale RCT to assess its clinical and economic effectiveness. Research Registry Unique Identifying Number: reviewregistry915.

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