Moreover, we identified 834 variant-trait associations primarily driven by the inclusion of participants from non-EUR populations; these associations were not even nominally significant in the EUR group (P > 0.05, table S9 ).
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Since changes of the methylation patterns appeared to be dominant in the field effects, we identified the nominally significant pathways with the methylation enrichment p-values < 0.05.
Results: In study 1, four SNPs showed nominally significant association ( P ≤0.05) with OS; two of these SNPs (rs1126647, rs4073) in IL8 were associated ( P ≤0.05) with OS in study 2.
A small proportion of associations and interactions with sex were nominally significant at P < 0.05 but not the more conservative 0.001 threshold; these may reflect a degree of type-1 error.
For associations without this information reported in the umbrella reviews, we recorded the information necessary to make the appropriate calculations and classifications: total number of cases, largest study reporting a nominally significant result (P<0.05), 95% prediction intervals, I 2 value, Egger regression asymmetry test, and evidence of excess significance.
In total, 18 (CRNN, DDX3X/DDX3Y/DDX4, DESP, DHB4, DSG3, ELAF, GBP6, K1C14, K1C16, K2C1, LEG7, PKP1, PKP3, PLAK, SPR1A, SPR1B, SPR2A, and TGM1, Figure 2 ) of these 207 proteins were found to have nominally significant ( p < 0.05, Wilcoxon ranked sum test) differences in abundance levels between cases and controls.
We defined this set as cis -eQTLs identified in LCLs or transformed fibroblasts in GTEx ( FDR < 0.05), which were not even nominally significant ( P > 0.05) in GTEx breast tissue.
31 Throughout the text, we refer to results as ‘nominally significant’ if they meet the threshold of p < 0.05 prior to FDR correction.
Additionally, we examined the nominal P values of the tests to which we applied the FDR corrections, considering tests that were nominally significant ( P < .05) but did not meet the FDR correction to facilitate further exploration of possible gut microbial signatures.
If the MR analysis results were nominally significant ( P < 0.05), we considered that there might be a causal relationship between the intestinal flora and the lipids.
Tier 1 findings included putative causal associations from the main analysis, which were directionally consistent, at least nominally significant in all analyses and showed no evidence of pleiotropy, that is, the Egger intercept P value >0.05, whereas tier 2 included the remainder of putative causal associations from the main analysis.
Post hoc contrasts revealed that REM theta energy shows a negative statistical trend with the response of the anterior–superior hypothalamus (t = −1.81; p = 0.07) and a positive nominally significant association with the response of the posterior hypothalamus (t = 1.90; p = 0.05; Figure 2 A,B).
The resulting p -values were considered nominally significant at p < 0.05.
There are a total of 74 splicing sites were found to have associations with prostate cancer at the nominally significant level threshold (P < 0.05) with P-HEIDI > 0.01 in the Qi et al. cohort and 14 splicing sites in the GTEx V8 cohort.
In addition, we performed a variety of sensitivity analyses for significant or nominally significant results.We used Cochran’s Q test and MR multivariate residual sums and outliers (MR-PRESSO) test to calculate the potential heterogeneity, where p < 0.05 indicated the presence of heterogeneity [ 31 ].
These pathways are potential novel associations with the Target Disease, which we checked by measuring enrichment of nominally significant SNPs (p < 0.05) in those genes from among the Target GWAS.
While integrative analysis of pathways restored by the microbiota-targeted interventions did not yield any FDR-significant results in either sex, several nominally significant pathways ( p- value < 0.05) were observed, highlighting potential effects on developmental, signaling, and metabolic processes.
ClinVar data were downloaded as VCF (accessed 02.05.2022) and filtered for nominally significant single variants ( P < 0.05 in any phenotype model).
( 2020 ), significance was evaluated at the p < 0.1 threshold due to the conservative nature of the test, though most nominally significant relationships had p < 0.05.
Fisher’s exact test showed a significant overlap in the eGenes identified by either method when we considered nominally significant (p < 0.05) results, suggesting that these methods each detect similar cell-type-specific signals from bulk expression data.
All 15 representative traits remained nominally significant (p<0.05) and showed consistent effect directions between marginal and conditional analyses ( Supplementary file 1 ).
The conditional analysis shows that 45 (including 42 genes) out of the total 74 (~60.8%) unique associations are still nominally significant when conditioned on known GWAS variants ( p < 0.05, Supplementary Table S4 ).
Model 4 constrains the MZ pair correlation to be twice the correlation for DZ and sister pairs combined, and the comparison of the log-likelihoods with those of Model 2 shows that, except for Cirrocumulus , there was at least nominally significant evidence that the MZ correlations were more than twice the corresponding correlations for DZ and sister pairs combined (all p ≤ 0.05).
Leave-one-out Analyses To identify gene-based results driven by one or more variants, we applied the following leave-one-out strategy: 1- among the variants seen more than twice in our stage 1 sample (cases and controls together), we identified the variant with the lowest single-variant analysis p value whenever it is nominally significant (p < 0.05); 2- we removed this variant and performed the stage 1 gene-based test again.
After conducting heritability analysis across 139 immune traits, we identified 10 immune traits with significant heritability (FDR p < 0.05), and 23 other traits with nominally significant heritability (p < 0.05) in at least one ancestry group.