Although the observed sign concordance of 52% is not significantly different from a random pattern ( P = 0.40), we find 3.23 times more SNPs in this set of 506 SNPs that are nominally significant for SZ than expected given the distribution of the P values in the SZ GWAS results (raw enrichment P = 6.87 × 10 −10 ).
Excerpts
Of the 677 genes with SV-expression associations at p < 0.01 for 1 Mb region (linear model adjusting for covariates) across the CBTN cohort, 126 were also associated with patient overall survival ( p < 0.05, Cox incorporating histologic type) in the same direction (e.g., genes both higher with SV breakpoints and higher in patients with worse survival), representing a highly significant overlap ( p < 1E-9, chi-squared test, Fig. 5a and Supplementary Data 7 ).
The five most highly significant (FDR P = 1 × 10 −9 ) Gene Ontology (GO) terms for biological process relate to immune system activation and regulation (Supplementary Data 12 ).
Knowing that multigenic cRM represent 10% of all cRM (967/9720), 25/76 (i.e., 33%) corresponds to a highly significant three-fold enrichment ( p < 10 −9 ).
To corroborate this finding, we next performed co-localization studies and confirmed that extracellular colocalization of IgG with HEV ORF2 protein was statistically highly significant (p < 10E-10; Fig. 3a and Supplementary Fig. 2b ).
The top SNP rs2290400 is a highly significant eQTL ( P values < 10 −9 ) for two genes, GSDMB and ORMDL3 , in whole blood (as found on gTEX, Fig. 4 ).
1 ; interestingly, we found that this enrichment for low-specificity sgRNAs was less pronounced but remained highly significant ( p = 1.1e−9, Fisher’s exact test), showing that the signature of off-target effects can be disguised in noisy screens.
Among the targets of E2F8, 17 were present in the LP gene expression module (total 115 genes), including Gjb2 , Tmem150a , Wfdc2 , Maged1 , a statistically highly significant enrichment ( p = 1.68E-09 in a hypergeometric test) (Supplementary Fig. 13a ).
There was a highly significant location by population interaction ( p = 3 × 10 −9 , mixed linear model ANOVA) and differences were significant for pop3 vs. non-pop3 survival at Tohoku ( p = 0.041) and Miyazaki ( p < 0.020, mixed linear model ANOVA with Tukey multiple comparison test) (Supplementary Tables 2 – 5 ).
Importantly, PAX7 target gene repression was also found to be a significant biomarker of FSHD status in each of the five microarray FSHD muscle biopsy studies independently, leading to a highly significant repression of PAX7 target genes on meta-analysis (Fisher’s combined test p = 3.5 × 10 −9 , Fig. 3c ).
Given the large number (>1 × 10 7 ) of highly significant variants following multiple-testing correction ( p < 4.07 × 10 −9 ), we consider a Chi-Square value in or above the 75th percentile across all MESA participants as evidence of ancestry-differentiated allele frequencies.
All these reported associations remain highly significant even after accounting for multiple testing using Bonferroni correction and a stringent GWAS P -value threshold (nominally P = 5 × 10 −9 adjusted to 1 × 10 −9 for five individual GWAS).
For the 374 sex-DE genes (FD≥1.2, P ≤0.05) that were also tested in the ASD-DE analysis, we observe a highly significant positive correlation between the sex-differential and ASD-differential FDs ( r =0.30, P =5.7e-09, Fig. 2c ), as well as for the subset of genes differentially expressed at FD≥1.2 and P ≤0.05 in both comparisons ( r =0.29, P =5.7e-04, N =90 genes).
Specifically, we observed clusters of highly significant Single Nucleotide Polymorphisms (SNPs) proximal to S04_3657761 in Chr04 associated with the DW ( − log 10 P = 8.22) (Fig. 6c ; see the quantile-quantile plots in Fig.
For PET imaging, increasing MTV between T0 and T2 was highly significant for worse OS and PFS ( p = 6.678 × 10 −9 and p = 6.973 × 10 −6 ).
5e ), and the difference in means was overall highly significant ( p = 9.95 * 10 −9 , two-sided t -test based on the data in Fig. 5d ).
This effect was highly significant (mixed-effects regression, N =43, P =10 −8 , Fig. 2c,d , Supplementary Table 2 , triple interaction between reward, transition type and colour deviation difference).
4b and Supplementary Data 2 ), which is highly significant (Binomial Test P -value < 10 −8 ) and suggestive of their functional importance.
All of the heritability and correlation estimates were highly significant ( p < 1 × 10 −8 ).
In the present study, our much larger case number (4890 for ASD-related disorders) and the large number of missense mutations identified in TRIO (11 ASD cases, as compared to 1.07 cases expected for the same number of individuals in the general population) dramatically improved the statistics, leading to a highly significant whole genome association of TRIO with ASD-like syndromes ( P -value of < 1.96 × 10 −8 ; Supplementary Table 3 ).
8b , right), where the slope of the fit decreases by more than half in the resting as compared to the running state across all combinations of N t and L , yielding a highly significant difference (two-tailed, paired t -test; p = 2e − 8, t = 9.2, df = 19).
Regression analysis (see Methods) showed that this association is highly significant (Fig. 3f , p = 2.1e−08, R 2 = 0.51, n = 30).
6 and 7 a highly significant, strong correlation (Spearman’s rho = 0.81, P < 3.5 × 10 −8 ) between the total number of stem cell divisions in an organ and the lifetime risk in that organ was reported.
One of the significant signals for smoking status was from NCAM1 , index SNP rs7110863 (Wald test p = 1.6 × 10 −35 ), which was highly significant for smoking trajectory in the MVP (index SNP rs7126748; Wald test p = 4.2 × 10 −8 ).
Ingenuity Pathway Analysis (IPA) indicated the UPR as the most highly significant canonical pathway (−log ( p -value) = 7.37) followed by ER stress (−log ( p -value) = 3.93).