DataSheet_1_Pleiotropy Complicates Human Gene Editing: CCR5Δ32 and Beyond.xlsx

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Data_Sheet_1_Improved Estimation of Phenotypic Correlations Using Summary Association Statistics.PDF

Estimating the phenotypic correlations between complex traits and diseases based on their genome-wide association summary statistics has been a useful technique in genetic epidemiology and statistical genetics inference. Two state-of-the-art strategies, Z-score correlation across null-effect single nucleotide polymorphisms (SNPs) and LD score regression intercept, were widely applied to estimate phenotypic correlations. Here, we propose an improved Z-score correlation strategy based on SNPs with low minor allele frequencies (MAFs), and show how this simple strategy can correct the bias generated by the current methods. The low MAF estimator improves phenotypic correlation estimation, thus it is beneficial for methods and applications using phenotypic correlations inferred from summary association statistics.</p

Exhaustive two-dimensional GWAS-scan for epistasis identifies six significant interactions, representing four unique pairs, associated with the root length mean.

<p>¹Name of associated SNP(s) at the epistatic locus as on the Affymetrix single nucleotide polymorphism (SNP) chip (our abbreviation as Chromosome_PositionInBp);</p><p>²p-value for the interaction effect of the two loci in the epistatic GWA analysis [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005541#pgen.1005541.ref040" target="_blank">40</a>];</p><p>³Probability that the pair is a false-positive when accounting for the small sample-size (SS) [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005541#pgen.1005541.ref042" target="_blank">42</a>].</p><p>*R², phenotypic variance explained per pair.</p><p>Exhaustive two-dimensional GWAS-scan for epistasis identifies six significant interactions, representing four unique pairs, associated with the root length mean.</p

Four statistical epistatic interactions associated with mean root length.

<p>(A) The x- and y-axes represent the five <i>A</i>. <i>thaliana</i> chromosomes. The positions of the seven SNPs that are part of the four significant interacting pairs (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005541#pgen.1005541.t002" target="_blank">Table 2</a>) are indicated by a black dot. Solid lines indicate support for an interaction by more than one linked SNP and dotted lines indicate support by a single SNP. (B) Genotype-phenotype (G-P) map of the root means for the four genotype combinations constituting the interaction between the SNPs on chromosome 1 (17,257,526 bp) and chromosome 5 (15,862,026 bp). The major allele is indicated by -1, and the minor allele is indicated by 1. This G-P-map is a representative example for the other pairs in which the accessions with a minor and major allele have lower phenotypic values than those with either both major or both minor alleles (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005541#pgen.1005541.s003" target="_blank">S2 Fig</a>). (C) G-P map for the most significant epistatic pair illustrates how this type of epistasis cancels the additive genetic variance at the allele-frequencies observed for the two loci in the analyzed population of wild-collected <i>A</i>. <i>thaliana</i> accessions.</p

Significant variance-controlling loci in <i>Arabidopsis thaliana</i>.

a<p>Traits with <i>p</i>-value inflation 1.5 and SNPs with MAF 10% were excluded, and significance was determined by a Bonferroni corrected significant threshold with genomic control;</p>b<p>MAF (Minor Allele Frequency = 1 - LAF (Low-variance Allele Frequency);</p>c<p>Dist: Distance. A positive/negative distance value indicates that the leading SNP is to the right/left of the gene with the given ID;</p>d<p>The <i>p</i>-values are from GWA (Wilcoxon) and vGWA (Brown-Forsythe) scans after genomic control.</p

Estimated narrow (h²) and broad sense (H²) heritabilities of root length mean and variance in a population of 93 natural <i>A</i>. <i>thaliana</i> accessions.

<p>¹Estimated using ANOVA on accession,</p><p>²Estimated using the R/hglm package (hglm) by fitting a linear mixed model including both additive and epistatic kinship matrices as random effects,</p><p>³p-values from Wald tests for the heritability being larger than zero, and s.e. are the standard errors estimated via jackknife resampling.</p><p>The broad-sense heritability estimates obtained using the phenotypic variances within and between accessions (H² = V_G/V_P; ANOVA) and the genomic relationships of the accessions (H² = (V_A + V_AA)/V_P; hglm) were similar and intermediate. The narrow-sense heritability (h² = V_A/V_P), estimated based on the genomic relationships between the accessions, was negligible.</p

Differences in mean and variance for traits in the <i>FRI</i>-<i>FLC</i>-flowering pathway.

a<p>Flowering-times LD (Long days), SD (Short days), V (Vernalization); ***/**/*/n.s.: ///non-significant in significance test for.</p>b<p>difference in mean (Wilcoxon) and</p>c<p>difference in variance (Brown-Forsythe) between <i>FRI</i>-genotypes;</p>d<p>s.d.: Phenotypic standard deviation;</p>e<p>CV: Coefficient of variation;</p>f<p>: Proportion of the phenotypic variance () due to the mean-controlling effect of <i>FRI</i> on the trait;</p>g<p>: Proportion of the phenotypic variance due to the variance-controlling effect of <i>FRI</i> on the trait.</p

image_1_Association between constipation and major depression in adult Americans: evidence from NHANES 2005–2010.tif

ObjectiveCurrent studies on the association between constipation and depression is still insufficient. In this study, we investigated the detailed association between constipation and major depression among American adults.MethodsIn this cross-sectional study, 12,352 adults aged 20 and older were selected from the National Health and Nutrition Examination Survey 2005–2010 for the sample. Constipation was defined as fewer than three defecation frequencies per week. For the assessment of major depression, the validated Patient Health Questionnaire-9 was used. Adjusted odds ratios (ORs) were calculated using multivariate logistic regression models. A subgroup analysis was carried out to ensure that the results were stable.ResultsOf the 12,352 participants, 430 reported constipation, with a prevalence of 3.5%. Depression was reported in 1030 cases, indicating a prevalence rate of 8.3%. Patients with constipation were significantly more likely to have major depression (20.9%) than those without it (7.9%, p  0.05).ConclusionIn conclusion, this study showed that constipation were significantly associated with depression. When treating patients with constipation, it is necessary for clinicians to screen and evaluate depression, and provide timely and effective intervention for patients with depression to avoid further deterioration of the condition.</p

Comparison of <i>p</i>-values (a) and proportions of the phenotypic variance explained (b) for loci detected in the GWAS and vGWAS.

<p>Wilcoxon and Brown-Forsythe tests were applied for the GWAS and vGWAS analyses, respectively. Plotted GC-corrected p-values are for the association of all SNPs with MAF for all the quantitative traits with -value inflation . The red dashed lines indicate the Bonferroni-corrected significance threshold. The scatterplots are heat maps for the logarithm of the number of dots in each mesh cell. A sub genome-wide significance threshold of is marked in (a), and a cutoff of 15% is marked in (b). The value in each block shows the ratio of the number of points in the block to the total number of points in the subfigure.</p

Data_Sheet_1_Correlation Between Proprioceptive Impairment and Motor Deficits After Stroke: A Meta-Analysis Review.pdf

Introduction: Proprioceptive impairment is a common symptom after stroke. Clarifying how proprioception correlates with motor function after stroke may be helpful in optimizing proprioception-augmented movement training. Previous studies have shown inconsistent findings. A meta-analysis is an optimal method to explore the correlation and identify the factors contributing to these inconsistencies.Objective: To explore the correlation between proprioception and motor function after stroke through a meta-analysis, taking into account characteristics of the measurements used in these studies.Methods: We searched multiple databases until November 2021 for eligible studies that measured both proprioception and motor functions in persons with stroke and reported their correlation or data for correlation analysis. A meta-analysis of the correlations was performed. The subgroup analysis and meta-regression were further conducted to investigate potential factors contributing to the heterogeneity of correlation strength, based on the participants' characteristics, proprioception, and motor function measures.Results: In total, 28 studies comprising of 1,829 participants with stroke were included in the meta-analysis. The overall correlation between proprioception and motor function was significant (r = 0.267, p 2 = 45%, p Conclusion: There is a significant correlation between proprioception and motor dysfunction after stroke. The proprioception measured in the axial segment under weight-bearing conditions or measured with ipsilateral matching, and motor function, specifically in the ICF domains of movement function, activity performance, and independence showed a positive contribution to the association between proprioception and motor function. The correlation does not imply causation and might be underestimated by attributes of current tests for proprioception and motor function. Further studies are needed to clarify the cause-effect relationship.</p