In our application, we prioritized nominally significant pleiotropic SNPs that achieved genome-wide significance ( P < 1.67 × 10−8) in the multi-trait analysis and suggestive significance ( P < 1 × 10 −3 ) in the original single-trait GWAS.
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Of 47 nominally significant species fecal butyrate associations, community modeling predicted the sign correctly for 43 associations (prediction accuracy: 91.49%, Fisher’s exact test: p = 1.69e-08).
For menstrual fever (QOL impact), we observed a nominally significant association signal at chr6:154.33–154.46 Mb (top SNP: rs17181171; P = 1.98 × 10 −8 ) that overlaps over half of the 5′-end of the opioid receptor mu 1 ( OPRM1 ) gene (Fig. 5a ) and contains 65 high LD SNPs (Supplementary Worksheet S6).
In the meta-analysis, the rs3020789 showed a genome-wide significant association and a nominally significant association for the male group ( β = –0.020; P = 2.12 × 10 −8 ) and female group ( β = –0.012; P = 0.024).
We observed a nominally significant finding (p = 2.9E-08, λ = 1.027 - corrected p gc = 2.2E-07, λ = 1.0015) on chromosome 6q21 in the gene coding for the non-receptor protein-tyrosine kinase, Fyn.
Also, for the women-only primary analysis, the rs77186623 in LOC105375745 locus associated with HIPadjBMI (β = −0.006, P = 1.74 × 10 −7 ) exhibited nominally significant interaction by background group ( I 2 = 55.3%, P diff = 0.042) and was GWS in the Caribbean group ( N = 3231, MAF = 0.041, β = −0.0078, P = 3.05 × 10 −8 ) but not significant in the mainland group ( N = 4216, MAF = 0.008, β = −0.0015, P = 0.567, Supplementary Material, Table S7 ).
This SNP was in linkage disequilibrium with two other SNPs that were nominally significant rs78201023 (MAF = 0.0393, p = 4.01 × 10 −8 , D ’ = 0.897) and rs77512118 (MAF = 0.0372, p = 1.37 × 10 −6 , D ’ = 0.908).
We first identified all SNPs within 10 000 kb of a nominally significant ( P -value < 5 × 10 −8 ) GWAS locus with r 2 > 0.6 in the 1000G EUR population to the index SNP, using PLINK 1.9.
We considered SNPs with a one-tailed p < 0.05 in our primary sample to be nominally significant; in the overall meta-analysis, SNPs with a two-tailed p < 5.00 × 10 −8 was considered genome-wide statistically significant.
Including rs74653330 (p.Ala481Thr), a missense lead variant in OCA2 , a total of 12 independent nonsynonymous variants associated with skin color traits were identified in the GWAS (Supplementary Data 5 ): 1 in a previously unreported locus, 9 in previously reported loci, and 2 in nominally significant loci (top variants of 2 loci did not pass the genome-wide significance level, P < 5.0 × 10 −8 ).
It was immediately clear from the sample size that even for minor allele frequencies (MAF) above 20% we would find at best nominally significant evidence for associations from this study alone (0.05 > p ≥ 5 × 10 −8 ; [ 33 ]).
Among the nominally significant associations, the most prominent was rs138558907:C > T near CCSER2 (OR: 13.04, 95% CI: 5.15–33.03, p = 6.1 × 10 − 8 , Table 2 ).
The identified lead SNP rs3732593 was extremely significant (P = 7.19 × 10 −8 ) in the discovery FHS sample but was only nominally significant (P = 0.04) in the replication sample.
Consistently, we found nominally significant associations with risks of both, myeloid (log(OR) = 1.52, P = 9.5 × 10 −8 ) and lymphoid (log(OR) = 1.38, P = 3.1 × 10 −7 ) leukaemia, but also multiple myeloma (log(OR) = 1.07, P = 5.1 × 10 −5 ) and non-Hodgkin lymphoma (log(OR) = 0.81, P = 4.7 × 10 −4 ).
We observed nominally significant enrichment of neuroticism GWAS variants within the osteoclast eQTL dataset at the P < 1 × 10 −7 and 1 × 10 −8 thresholds ( P = 0.01 and 0.007, respectively, Fig. 2 ); however, these were not significant after correction for multiple testing.
In the WHI, all but one of the 1000 cis CpG-transcript pairs from discovery in FHS replicated at a nominally significant p -value of 0.05 with matching effect directionality, while 997 replicated at p < 1E−7 with matching effect directionality.
Polygenic risk score (PRS) computation SNPs of PRS include: 1) SNPs that are statistically significant or nominally significant per GWAS threshold ( p < 1.0 × 10 − 7 and p < 1.0 × 10 − 6 , respectively) and exome sequencing analysis ( p < 9.2 × 10 − 7 and p < 9.2 × 10 − 6 , respectively) [ 14 ]; 2) Index SNPs or Proxy SNPs in 1 Mb region that were statistically significantly and nominally significantly associated with bone health ( p < p value threshold and p < 0.05, respectively).
Only the mastectomy GWAS failed to yield nominally significant SNP hits ( P <10 −7 ).
Four genetic variants were found to be nominally significant (p-value < 1 × 10 −7 ) in this GWAS of 163,985 women 22 .
SNP rs36259 is an exonic non-synonymous SNP located in the CERS4 gene which achieved close to genome-wide significance ( p = 6.270e−08) and was nominally significant in our original study ( p = 1.69e−7).
Nominally significant associations were also observed for ‘Age when periods started (menarche)’ ( P = 1.7 10 -7 ), ‘Non-cancer illness code, self-reported: endometriosis’ ( P = 3.8 10 -7 ), ‘Part of a multiple birth’ ( P = 4.6 10 -7 ), supporting the findings from the GWAS catalogue look-up.
In agreement with the LDA approach, the differential expression analysis revealed a nominally significant increase in the expression of RvE3 in pwALS at baseline compared to NNC (nominal P = 1.91 × 10−07), an upregulation seen in all pwALS phenotypes (1.33 × 10−06 < nominal P < 0.00314).
All CpG sites, except one site (cg21161138) near AHRR , remained nominally significant (3.17 <| z |< 5.19, 1.52e − 03 < p < 2.10e − 07) with the same direction of association in the sensitivity analysis adjusted for smoking (Additional file 1: Table S1 and Fig.
Although they did not survive false discovery rate correction (FDR) for multiple testing (Additional file 1 : Table S3), the nominally significant pairwise comparisons showed enrichment for π c differences related to hematological and metabolic traits (hematological fold-enrichment = 4.45, p = 2.15 × 10 –7 ; metabolic fold-enrichment = 4.05, p = 4.01 × 10 –6 ).
( 23 ) and another two SNPs were nominally significant including rs11556924 ( p = 3.3e-07, locus 10) and rs2980853 ( p = 3.5e-05, locus 11). 3.2.3.