First, exposure‐outcome associations that were nominally significant ( P < 0.05) on primary analysis with IVW MR were identified.
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p=0.08
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We did, however, observe nominally significant correlations ( p -value < 0.05) between other pairs of tested neurodegenerative diseases, except for FTD, for which there were no nominally significant correlations (Supplementary Table 1 ).
In addition, there was substantial enrichment of nominally significant associations ( p <0.05) among disease SNPs.
We defined significant novel associations as those that were at least nominally significant in replication (P<0.05) with consistent direction of effect and had an overall P < 5×10 −8 (genome-wide significance) in the discovery and replication cohorts combined.
Although the proteomic profiles of the 21 cyclophosphamide responders versus 14 non-responders overlapped by PCA ( Supplemental Data S3 ; Document S1 : Data S1 B, Figure S2 ; Tables S4 and S5 ), several immune-related proteins (e.g., IGHE, KIT, CD80, and IL-34) showed nominally significant differences ( p < 0.05), none of which remained significant after FDR correction.
The Radial plot method was used to select eligible resting heart-rate associated genetic variants for fitness by removing heterogeneous outliers for the genetic variants, of which 149 were also nominally significant in the fitness GWAS ( p < 0.05) [ 28 ].
Finally, to characterize the functional relevance of genes driving the association between effects of LPS on MR imaging measures and expression of cell-type specific genes, we ran a Gene Ontology analysis using genes that were: (i) nominally significant p < 0.05 (MR imaging measure vs. gene expression correlation), and (ii) within the 10th decile in cell specificity for a given cell type (IT4/5 excitatory, or Parvalbumin inhibitory).
Depending on the model type selected, between 8% and 19% of protein pairs exhibited a nominally significant correlation ( P < 0.05) between predicted and observed expression/co-expression in all three models, but this percentage rose to over 99% in well-imputed pairs.
All showed a concordant effect direction between the GWAS prospective and GWAS retrospective (p=0·0005, binomial sign test), with six loci nominally significant (GWAS prospective p<0·050) and one significant after Bonferroni correction for the 12 loci (rs3851357, GWAS prospective p=0·0035).
We detected nominally significant changes in PC1 in the semaglutide group and in PC5 in the empagliflozin group (repeated measures ANOVA, p ≤ 0.05).
Differences between groups were nominally significant (nominal P < 0.05) if the 95% confidence interval [CI] of the group difference did not include the null value (0 for mean differences and 1 for odds ratios), but for the sake of convenience, if the nominal P ‐value in the secondary analysis is less than 0.05, it is described as significant, and if it is 0.05 or more, it is described as non‐significant.
Smoothed methylation values over nominally significant ( p < 0.05) DMRs from each comparison were obtained using the “getMeth” function in the bsseq R package v1.36.0.
In total, 15,803 transcripts, including both coding and non-coding transcripts were measured with sufficient coverage in both samples, of which 503 were found to have nominally significant differential expression (p<0.05), which after correction for multiple hypothesis a total of 35 were considered significantly expressed (p<0.05, Benjamini-Hochberg) ( Sup.
Specifically, we identified a total of 169 nominally significant enriched terms ( p -value < 0.05 and FDR < 0.2), which represent a medium-confidence set, including a subset of 37 high-confidence terms that passed multiple test correction with an FDR of <0.05 ( Figure 3 ).
To verify the reliability of these polygenic associations, we repeated the analyses using PRS comprising only the 108 sentinel genome-wide significant schizophrenia variants 15 , based on the assumption that the effect size estimates of genome-wide significant variants should be less affected by population structure than non-significant variants; 77 of the 104 associated traits were nominally significant ( P < 0.05) based on the PRS comprising only genome-wide significant variants.
Because we detected a nominally significant difference (p = 0.05) in the amount of fruit consumed by the members of Mica's group (7.9%, 95% CI: 0.0–8.3%) and the members of Viola's group (2.2%, 95% CI: 1.0–7.3%) during the sampling period, we also compared our results to a published data set of seasonal differences in gut microbiome composition in humans ( Davenport et al., 2014 ).
In a per-protein analysis, replacing values below the limit of detection with protein specific LOD-values, five proteins (CSF-1, NTRK3, ICOSLG, SCF and PECAM-1) were found to have nominally significant differences between the two time-points (p < 0.05, Wilcox test).
Variable Selection Based on linear mixed models including the factors of time, age at enrollment, sex, and stimulus version, 23 speech variables from the picture description task showed nominally significant ( P < 0.05) effects of time at the group level.
DHX58 and SWAP70 showed protein‐level associations with CAD (FDR <0.05) and colocalization probabilities between 0.5 and 0.7, with nominally significant associations ( P <0.05, unadjusted) at the methylation and expression levels.
For CD4 + T cells, baseline β7 integrin expression had a nominally significant (unadjusted p < 0.05) effect on the following genes: ITGA4, GATA3, GZMA, BATF, HIFA, ICOS and IRF4, although none of these genes had an FDR below 0.1.
Multivariable modelling and the relations between predictor variables All predictor variables having shown nominally significant (p < 0.05) effects on hand preference in univariable testing (i.e. all but maternal smoking) were then included in the multivariable analysis, using general linear modelling (Methods), with hand preference as the dependent variable.
Fourteen MGSs were nominally significant for the broad spectrum (Wilcoxon signed-rank test, unadjusted p < 0.05).
We note that although APOE has previously been identified as a AD TWAS gene in microglia 83 , we did not highlight it in our scTWAS results because it did not pass Stage 1 screening, despite nominally significant Stage 2 associations in proliferate, surveilling, and reacting microglia (nominal p -values < 0.05).
Results: In primary data, nominally significant ( P < 0.05) differential methylation between groups was observed for over 100 CpG sites, including genes involved in immunomodulation of the NF-kappaB inflammation pathway, endocannabinoid signaling, and inflammatory mediator regulation of TRP channels.
So it should be kept in mind that each individual p value has a one-in-twenty chance of being nominally significant (p < 0.05) purely from random fluctuations.