scholarly journals Mapping oligogenes for atopy and asthma by meta-analysis

2000 ◽  
Vol 23 (1) ◽  
pp. 1-10 ◽  
Author(s):  
A. Collins ◽  
S. Ennis ◽  
W. Tapper ◽  
N.E. Morton
Keyword(s):  
Alternative Hypothesis ◽  
Rank Order ◽  
Meta Analysis ◽  
Genetic Effect ◽  
Allelic Association ◽  
Type I ◽  
A Genome ◽  
Significance Levels ◽  
Complex Inheritance ◽  
Candidate Regions

Meta-analysis is presented for published studies on linkage or allelic association that have in common only reported significance levels. Reporting is biassed, and nonsignificance is seldom quantified. Therefore meta-analysis cannot identify oligogenes within a candidate region nor establish their significance, but it defines candidate regions well. Applied to a database on atopy and asthma, candidate regions are identified on chromosomes 6, 5, 16, 11, 12, 13, 14, 7, 20, and 10, in rank order from strongest to weakest evidence. On the other hand, there is little support for chromosomes 9, 8, 18, 1, and 15 in the same rank order. The evidence from 156 publications is reviewed for each region. With reasonable type I and II errors several thousand affected sib pairs would be required to detect a locus accounting for 1/10 of the genetic effect on asthma. Identification of regions by a genome scan for linkage and allelic association requires international collaborative studies to reach the necessary sample size, using lod-based methods that specify a weakly parametric alternative hypothesis and can be combined over studies that differ in ascertainment, phenotypes, and markers. This has become the central problem in complex inheritance.

scholarly journals Common risk variants identified in autism spectrum disorder

2017 ◽  
Author(s):  
Jakob Grove ◽  
Stephan Ripke ◽  
Thomas D. Als ◽  
Manuel Mattheisen ◽  
Raymond Walters ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Complex Disorders ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
A Genome ◽  
Significance Levels ◽  
Near Term

AbstractAutism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 ASD cases and 27,969 controls that identifies five genome-wide significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), seven additional loci shared with other traits are identified at equally strict significance levels. Dissecting the polygenic architecture we find both quantitative and qualitative polygenic heterogeneity across ASD subtypes, in contrast to what is typically seen in other complex disorders. These results highlight biological insights, particularly relating to neuronal function and corticogenesis and establish that GWAS performed at scale will be much more productive in the near term in ASD, just as it has been in a broad range of important psychiatric and diverse medical phenotypes.

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.

Power-Cost Efficiency of Eight Macrobenthic Sampling Schemes in Puget Sound, Washington, USA

1989 ◽  
Vol 46 (12) ◽  
pp. 2157-2165 ◽  
Author(s):  
Steven P. Ferraro ◽  
Faith A. Cole ◽  
Waldemar A. DeBen ◽  
Richard C. Swartz
Keyword(s):  
Cost Efficiency ◽  
Statistical Power ◽  
Rank Order ◽  
Puget Sound ◽  
Sampling Scheme ◽  
Total Biomass ◽  
Type I ◽  
Power Cost ◽  
Sampling Schemes ◽  
Sample Unit

Power-cost efficiency (PCEi = (n × c)min/(ni × ci), where i = sampling scheme, n = minimum number of replicate samples needed to detect a difference between locations with an acceptable probability of Type I (α) and Type II (β) error (e.g. α = β = 0.05), c = mean "cost," in time or money, per replicate sample, and (n × c)min = minimum value of (n × c) among the i sampling schemes) is the appropriate expression for comparing the cost efficiency of alternative sampling schemes having equivalent statistical rigor when the statistical model is a redistribution for comparisons of two means. PCEs were determined for eight macrobenthic sampling schemes (four sample unit sizes and two sieve mesh sizes) in a comparison of a reference site versus a putative polluted site in Puget Sound, Washington. Laboratory processing times were, on average, about 2.5 times greater for the [Formula: see text]- than the [Formula: see text] samples. The 0.06-m2, 0- to 8-cm-deep sample unit size and 1.0-mm sieve mesh size was the overall optimum sampling scheme in this study; it ranked first in PCE on 8 and second on 3 of 11 measures of community structure. Rank order by statistical power of the 11 measures for this scheme was Infaunal Index > log10 (mollusc biomass + 1) > number of species > log10 (numerical abundance) > log10 (polychaete biomass + 1) > log10 (total biomass + 1) > log10 (crustacean biomass + 1) > McIntosh's index > 1 – Simpson's Index > Shannon's Index > Dominance Index.

The Robustness of the Likelihood Ratio Chi-Square Test for Structural Equation Models: A Meta-Analysis

2001 ◽  
Vol 26 (1) ◽  
pp. 105-132 ◽  
Author(s):  
Douglas A. Powell ◽  
William D. Schafer
Keyword(s):  
Structural Equation ◽  
Structural Equation Models ◽  
Type I Error ◽  
Meta Analysis ◽  
Generalized Least Squares ◽  
Error Rates ◽  
Type I ◽  
Chi Square ◽  
Distribution Free ◽  
Projection Techniques

The robustness literature for the structural equation model was synthesized following the method of Harwell which employs meta-analysis as developed by Hedges and Vevea. The study focused on the explanation of empirical Type I error rates for six principal classes of estimators: two that assume multivariate normality (maximum likelihood and generalized least squares), elliptical estimators, two distribution-free estimators (asymptotic and others), and latent projection. Generally, the chi-square tests for overall model fit were found to be sensitive to non-normality and the size of the model for all estimators (with the possible exception of the elliptical estimators with respect to model size and the latent projection techniques with respect to non-normality). The asymptotic distribution-free (ADF) and latent projection techniques were also found to be sensitive to sample sizes. Distribution-free methods other than ADF showed, in general, much less sensitivity to all factors considered.

Do sexist jokes increase rape proclivity among males high in hostile sexism? Evidence from two pre-registered direct replications of Thomae & Viki (2013)

2021 ◽  
Author(s):  
Neil McLatchie ◽  
Manuela Thomae
Keyword(s):  
Bayes Factor ◽  
Alternative Hypothesis ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Original Study ◽  
Bayes Factors ◽  
Hostile Sexism ◽  
Replication Studies ◽  
Open Research ◽  
Rape Proclivity

Thomae and Viki (2013) reported that increased exposure to sexist humour can increase rape proclivity among males, specifically those who score high on measures of Hostile Sexism. Here we report two pre-registered direct replications (N = 530) of Study 2 from Thomae and Viki (2013) and assess replicability via (i) statistical significance, (ii) Bayes factors, (iii) the small-telescope approach, and (iv) an internal meta-analysis across the original and replication studies. The original results were not supported by any of the approaches. Combining the original study and the replications yielded moderate evidence in support of the null over the alternative hypothesis with a Bayes factor of B = 0.13. In light of the combined evidence, we encourage researchers to exercise caution before claiming that brief exposure to sexist humour increases male’s proclivity towards rape, until further pre-registered and open research demonstrates the effect is reliably reproducible.

Abstract 16003: Genetic Variation Associated With Favorable Exercise Response in Patients With Systolic Heart Failure: A Hf-action Trial Substudy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sara Coles ◽  
Stephanie Giamberardino ◽  
Carol Haynes ◽  
Ruicong She ◽  
Hongsheng Gui ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Trial ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Systolic Heart Failure ◽  
Genome Wide Association ◽  
Supervised Exercise ◽  
Genome Wide ◽  
A Genome ◽  
Response To Exercise

Background: Exercise has shown benefit in patients with systolic heart failure, including in the clinical trial Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION). There is heterogeneity in who derives benefit from exercise, and the biologic mechanisms of favorable response to exercise in systolic heart failure are not well understood. Hypothesis: Genetic variation is an underlying factor influencing heterogeneity in response to exercise in patients with systolic heart failure. Methods: The HF-ACTION trial randomized individuals with systolic heart failure (left ventricular ejection fraction <35%) to supervised exercise versus usual care. In this study, we performed a genome wide association study (GWAS) in the HF-ACTION biorepository using the Axiom Biobank1 genotyping array (13,403,591 single nucleotide polymorphisms [SNPs] after quality control on directly genotyped and 1000 genomes imputed data), in N=377 study subjects who completed the supervised exercise arm. Using change in peak VO2 as our outcome, we ran within-ancestry GWASes, modeling SNP effects as both additive and dominant, and conducted across-ancestry meta-analysis within each genetic model. Results: Five loci met genome-wide significance in the European ancestry analyses, 5 loci in the African ancestry, and 8 in the meta-analyses. The two most significantly associated loci across both additive and dominant meta-analysis models were rs111577308 located in the histone acetylation for transcription elongator complex 3 gene ( ELP3, p=1.212x10 -9 ) and rs75444785 located in the phosphodiesterase 4D gene ( PDE4D , p=1.565x10 -9 ). ELP3 is responsible for histone modifications related to DNA transcription factor complexes, and PDE4D is involved in cyclic AMP cell signaling. In silico analysis of these loci showed that they are in linkage with regions associated with skeletal muscle and peripheral vascular disease phenotypes. Conclusions: Using a genome-wide association study in a well-phenotyped clinical trial of exercise in systolic heart failure, we found common genetic variants in genes involved in DNA transcription histone modification and cyclic AMP cell signaling that are associated with a more favorable response to exercise.

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