However, 12 out of 245 CpG sites showed nominally significant differences ( p < .05) between pre‐ and post‐menopausal women.
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For all nominally significant associations (P < 0.05), we conducted a Bayesian colocalisation analysis to determine whether GWAS and expression quantitative trait locus (eQTL) signals shared a causal variant [ 40 ].
First, exposure‐outcome associations that were nominally significant ( P < 0.05) on primary analysis with IVW MR were identified.
In addition, there was substantial enrichment of nominally significant associations ( p <0.05) among disease SNPs.
Twelve CpG sites had nominally significant associations with the overall breast cancer incidence risk ( P < 0.05), and four of them passed the multiple-testing correction (Bonferroni P < 0.05/59 = 8.47 × 10 –4 ).
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 ].
According to BADGERS, the reference panel comprises 1738 traits from the UKB 17 , selected on the basis of nominally significant SNP-based heritability ( P < 0.05).
Only associations with at least a nominally significant P value ( P < 0.05) were selected for further evaluation as potential mediators.
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).
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.
Also, the association between sentinel variants in the FoxP1 gene and diagnosis of IPF was nominally significant ( p < 0.05) rather than genome-wide significant.
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.
Five SNPs showed evidence for nominally significant ( P < 0.05) association with the same direction of effect as the discovery cohort, compared with 1.35 under the null expectation (binomial test P = 0.01; Supplementary Table 4 ). rs143384 reached genome-wide significance in the replication dataset alone (effect allele A, EAF 0.61, OR [95% CI] 1.37 [1.24–1.51], P = 1.33 × 10 −10 ).
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.
Gene-based analysis revealed 76 nominally significant ( p ≤ 0.050) longevity-associated genes, and we call these 76 genes the “longevity-associated gene set” (Tables S3 and S4 ).
The first 10 PCs were included in FG and FI analyses, and nominally significant PCs ( P <0.05) were added in T2DM analyses.
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 ).
When assessing the relationship between the six individual stress domains and the nine CpG sites, we found that acute life events, financial stress, and lifetime discrimination domains had at least nominally significant associations with all CpG sites ( p < 0.05), while neighbourhood stress, relationship stress, and childhood adversity each had nominal associations with at least six CpG sites (Supplemental Table S5).
Fourteen MGSs were nominally significant for the broad spectrum (Wilcoxon signed-rank test, unadjusted p < 0.05).
Some nominally significant correlations (uncorrected p < 0.05) were also observed in AN and BN groups (details in the Online Supplementary Material, Tables S1-S3).
In all, 1,608 specifications comprised more than a single study, yielding 1,363 (85%) nominally significant ( p < 0.05) negative and 9 (<1%) significant positive summary effects.
Using a nominally significant cut-off (cor > 0.50, p < 0.05), nine module-trait relationships emerged ( Figure 3d ).
These sets were gene ontology terms: “negative regulation of transforming growth factor beta production,” “negative regulation of transforming growth factor beta1 production,” “MHC class I peptide loading complex,” and “TAP complex binding.” We also conducted an ORA to test if a higher proportion of genes from any gene set showed a nominally significant (uncorrected P -value <0.05) association with the life history traits ( supplementary data S5, Supplementary Material online).
Of these, 10 had significantly different effect sizes ( p -value < 7.8 × 10 −4 , Bonferroni correction for 64 variants) and 22 were nominally significant ( p -value < 0.05).
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.