For instance, while only the association between brain network connectivity and AF survived Bonferroni correction ( P < 2.62 × 10−4), several other phenotypes showed nominally significant associations ( P < .05) with CVDs, and also, to more flexibly balance the Type I and Type II errors, We applied a false discovery rate control to the results of all IVW methods (Table S4, Supplementary Digital content, https://links.lww.com/MD/P315 ).
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23 We specifically identified outcomes for which meta-analyses of observational studies showed nominally significant associations (at P≤0.05), did not have large between study heterogeneity, were based on evidence from more than 500 cases (or more than 5000 total participants if the type of metric was continuous), and showed no evidence of small study effects or excess significance.
Nominally significant ( P < 0.05) associations with gout were detected at CARD8 rs2043211 (OR = 1.12, P = 0.007), IL1B rs1143623 (OR = 1.10, P = 0.020) and CD14 rs2569190 (OR = 1.08; P = 0.036) .
The remaining nominally significant associations ( p < 0.05) were considered to provide “weak” evidence.
Among them, 59 immunophenotypes exhibited a nominally significant causal association with TMD (IVW, P < 0.05).
To further test for potential pleiotropic effects of non-psychiatric diseases, we performed a phenomewide association study on all nominally significant (P<0.05) SNP instruments within all Bonferroni-significant genes using the IEU OpenGWAS database 16 , 17 , filtered using the keywords “cancer” and “disease.” An extensive literature search was performed to determine potential novelty of significant MR results ( eMethods ).
Among the ten CpG sites significantly associated with self-reported antidepressant use reported from the Generation Scotland cohort 14 , two of them (cg03864397 annotated to CASP10 implicated in innate immune response, b = − 0.23, p = 0.03; cg26277237 annotated to KANK1 , b = 0.24, p = 0.03) were nominally significant in this meta-analysis ( p < 0.05) and with consistent direction in effect size (Supplementary Table 5 ).
Assessment of differentially methylated regions Nominally significant probes ( p ≤ 0.05; n = 24,149) were included in the differentially methylated region (DMR) analysis, identifying 123 DMRs ( q ≤ 0.05; Supplementary Table 5 ).
Genetic pathway analysis We identified a gene set by selecting all genes showing nominally significant expression changes ( P ≤ 0.05) in our data set, and we tested if our gene set was enriched for associative signal with two phenotypes: (i) hippocampal volume in adults; (ii) antidepressant response.
If flanking regions were reduced to ±10kb, PXN (±10kb) remained significantly associated with alcohol dependence in EAs ( p <E-8), and the other 19 top-ranked risk genes remained nominally significant ( p <0.05).
Five of the 19 SNPs demonstrated a nominally significant association with neovascular AMD (P < 0.05), of which two (rs3173798 and rs3211883) withstood Bonferroni correction for multiple testing (rs3173798, nominal P = 9.96 × 10−4, allele-specific odds ratio = 0.55; rs3211883, nominal P = 2.09 × 10−4, allele-specific odds ratio = 0.50).
To underpin this, we further checked the directions of effect of all nominally significant a-DMSs ( P < 0.05) and found that methylation changes tended to be negatively associated with maternal smoking between 0 and 4/5 years (Fig. 4b ) and, moreover, that 721/971 (74.2%) a-DMSs showed a stronger decrease in methylation levels from 0 to 4/5 years (Additional file 1 : Table S7).
Overall, 30 of the 48 (63%) associations reported a nominally significant summary result at p<0.05 (19 had p≤0.001).
The chemokine MCP3 showed a nominally significant association with ischemic stroke risk (OR: 0.93, 95% CI: 0.88–0.99, unadjusted p < 0.05).
Under the assumption that the gap statistic follows a standard normal distribution, approximate p-values for all three analyses were nominally significant (p < 0.05), with the blood and dura analysis resulting in the most significant gap statistics (p < 1×10 -10 ).
Combinations demonstrating nominally significant inter-group differences ( p < 0.05) were selected for further exploratory analyses (n = 25 for 3-antigen, n = 31 for 4-antigen, and n = 25 for 5-antigen combinations).
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.
The global analysis revealed only a modest transcriptomic signal associated with suicide, with ten nominally significant DEGs identified at the predefined threshold ( p < 0.05 and |logFC| > 0.15), although none remained significant after FDR correction ( CKS2 , PDE2A , TYROBP , H2BC12 , TMED1 , EPCAM , ADORA3 , EGR3 , NR4A2 , and NEUROD6 ).
Nominally significant eQTLs ( P < 0.05) were not seen for MYC ( P = 0.29) or for the SNPs on chr5p15.33 ( P = 0.91 for CLPTM1L ; TERT was not expressed) or 1q32.1 ( P = 0.68 for NR5A2 ).
CSF Markers and Clinical Variables Bivariate correlation analyses revealed a significant relationship between semantic fluency and α‐synuclein that withstood correction for multiple testing ( r = −0.53, P = 0.003) as well as nominally significant associations ( P < 0.05) between semantic fluency and IL‐6, ACE‐R and IL‐6, and age and both IFN‐γ and IL‐1β (Table S2 ).
The strength of the association between LoF+DCM burden and case status (at p=7.6e-15 without controlling for Vineland scores), is only nominally significant after Vineland score is controlled for (p=0.05).
A signal was considered to replicate if: i) it met our Bonferroni corrected gene-level significance threshold ( p <1.32x10 -7 ); ii) >2 variants were tested; iii) it was nominally significant ( p <0.05) in the unadjusted test for WGS (i.e. without adjusting for correlated traits).
A nominally significant association was observed between survival and the DPP4 enzymatic activity at day 1 (p ≤ 0.05), with a higher DPP4 enzymatic activity being associated with an increase in survival.
Variants that were nominally significant ( P < 0.05) and within 1000 kb and a r 2 > 0.1 of the sentinel SNPs were assigned to a locus.
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.