Specifically, the evidence grading criteria were as follows: If the association was supported by a highly significant random-effects ( P < 10−6, a threshold considered to substantially reduce false positive findings) 10 – 13 , a sample size of more than 1000 cases, P < 0.05 in the largest study, I2 < 50%, absence of small study effects, a PI excluding the null, no evidence of excess significance bias, and P < 0.05
Excerpts
No SNPs reached genome-wide significance, however four independent SNPs were nominally significant ( P < 1 × 10 −6 ) (Fig. 3 ).
GARFIELD reads variants from our GWAS summary statistics using two p -value thresholds: genome-wide significance ( p = 5 × 10 −8 ) and borderline significant ( p = 1 × 10 −6 ) in its analysis.
In Supplementary Data 6 , the association of CHRM3 activation with “urinary contraction” (literature ID 364) contains the p value and ROC AUC for “Urinary retention” and is classified as highly significant ( p ≤ 1e-06), with distance 1 (i.e., the significant PT and starting PT are connected via 1 intermediate in the network, via the shared HT).
All 157 SNPs with highly significant associations ( P <1 × 10 −6 ) in this region, were in high linkage disequilibrium with rs188686860 and rs115635831 ( r 2 >0.90), and were located proximal (Hg19: 201,717,014-201,995,860) to the CASP8 gene ( Supplementary Table 15 ).
This is a highly significant enrichment relative to the <3% of background genes with known interactions (Fisher’s test p < 10 −6 ), confirming that our analytical pipeline is an effective approach to enrich for druggable targets. 645 (34%) of the compounds are predicted in a single patient, ranging from 15 in patient 17 to 205 in patient 18, further highlighting the importance of a patient-specific approach (Fig.
Within these 47 regions, we also assessed whether the traits that did not have a variant with p < 5 x 10 − 8 , had a moderately significant variant with p < 1 x 10 − 6 ; signals from such traits were also included in our fine-mapping.
Image-based HSPC fractions showed highly significant concordance with the clinically determined peripheral blood (PB) blast percentages ( p < 1.06 −6 ; Supplementary Fig. 2d, e ).
These differences were highly significant for both Proteobacteria and Firmicutes (paired t -tests P = 1.4 × 10 −6 and P = 8.4 × 10 −6 , respectively).
Cluster 3 had multiple highly significant correlations (203, with an absolute value of rho ≥ 0.5 and P < 1.8 × 10 −6 ) including a group of proline-related metabolites (4-hydroxyproline, prolyl-hydroxyproline, and 4-hydroxyglutamate).
The single exception is Prs3-F[1,2]:Fpr1-F[3], which displayed a small but highly significant fitness advantage (fitness=0.04, P value <2 × 10 −6 , Bonferroni corrected one-sided Student's t -test) that is perhaps due to an adaptive mutation that occurred in the parental PCA strain before barcoding.
ANOVA across species was highly significant ( F (3,16.70) = 22.70), P = 3.97 × 10−6), post hoc tests (BH-adjusted) confirmed E. turneriana as significantly lower ( P < 0.01).
A post-hoc Games–Howell test (Tukey corrected p values), was used to compare each mutant genotype to the wt since this test is compatible with the highly significant inequality of variances (Levene’s test, p = 3.98 × 10 −6 ).
The perfect association between copy number of the duplicated sequence and the fast/slow greying phenotype including both Connemara ponies from Sweden and Thoroughbreds from Japan is highly significant (Fisher’s exact test; P = 4.9 × 10 -6 ) (Fig. 3c , Supplementary Fig. 4a , Supplementary Table 2 ).
After conditioning on the top variant rs4143332 (LD- r 2 of 0.988 to HLA-B*08:01 ), or complement component 4 ( C4 ) expression levels HLA-C*05:01 remained nominally significant (rs4143332: OR = 0.6869, P = 5.662e −6 , SE = 0.0828; C4 expression: OR = 0.68991SE = 0.0865, P = 1.774e −5 ), indicating partial independence from HLA-B*08:01 and C4 .
Calcium-dependent changes in r 1 observed for Mn L1 and Mn L3 in the presence of BAPTA are 105% and 23%, respectively; both are highly significant ( t -test p < 7 × 10 −6 ).
When malnourished children were defined as either stunted or anemic, the association between these taxa was highly significant ( n = 196, P = 9.5e-06, rho = 0.31), while the slight trend seen in nonstunted children disappeared entirely in children who were neither stunted nor anemic ( n = 112, P = 0.9925, rho = −0.001).
ESM-1b t s + ECFP) is statistically highly significant (McNemar’s test: p < 10 −5 ).
An initial Pearson correlation analysis indicated a highly significant association with Nonpareil diversity and pH ( R = 0.51, p < 1 × 10 −5 ), along with weaker correlations to several other parameters.
The diverging instrumental effects of DBP and SBP on migraine were also supported by restricting analysis to SNP instruments that were non-significant ( P > 0.05) for one measure but highly significant ( P < 1 × 10 −5 ) for the other (Supplementary Fig. 28 ).
The presence of clustered breakpoints on a per-chromosome basis 13 : chromosomes that had a highly significant non-random distribution of breakpoints with a stringent threshold of P < 10 −5 were considered to be clustered.
We found a highly significant increase in the KEGG and REACTOME cell cycle pathway enrichment scores (both p < 0.00001), supporting the cell cycle phase analysis results (Fig. 4c ).
In both cases, the calibration curves showed a highly significant linear response over a concentration range spanning two orders of magnitude ( R 2 > 0.99; p value < 10 −5 ; Fig. 3b, c ).
6b and 6f ) is highly significant ( p = 10 −5 ).
The interaction effects on breast cancer risk of these five TF pairs were all highly significant ( P < 1 × 10 −5 ; Supplementary Data 2 ).