Excerpts

While rs138740 did not replicate, it remained borderline significant (meta-analysis P =5.7 × 10 −8 ) when the discovery and replication sets were combined and we observed effects in the same direction as in the meta-analysis (OR=1.04–1.08; Table 2 ).

Due to time and cost constraints, we opted for haplotype-based mapping and obtained a highly significant ( P = 5.71 × 10 −8 ) and fine mapped QTL on OAR11 (CI 37,000,925–37,521,490 Mb) as well as another genome-wide significant result ( P = 1.08 × 10 −5 ) with less sharp mapping (OAR2, CI 93,441,900–96,402,884 Mb).

To the best of our knowledge, significant genome wide association for four of these loci are unreported in the context of de novo tinnitus (represented by rs7336872, rs115125870, rs1532898 and rs2537), with rs7336872 showing borderline significance in the study by Wells et al. 14 ( p = 5.9 × 10 –8 ).

Two other highly significant regions included a ten probe DMR in RHCG (Šídák -corrected P = 5.95 × 10 –8 ) and a nine probe DMR in COL18A1 (Šídák -corrected P = 9.39 × 10 –8 ).

The highly significant category was “regulation of protein kinase activity” (GO: 0045859) ( P = 5.95E-8) containing the candidate genes PCK1 and EDN3 ; another significant category was “transmembrane receptor protein tyrosine kinase signaling pathway” (GO: 0007169) ( P = 5.80E-9).

The test revealed a highly significant reduction in prediction error with the hybrid approach ( p = 5.97 × 10−8).

Despite the small sample size, the burden of association between BMPR2 and PAH was highly significant ( p = 6.0 × 10 −8 ) compared to the genome-wide significance threshold ( p < 2.4 × 10 −6 ) after Bonferroni correction for approximately 21,000 genes (Fig. 2 ).

This is supported by a highly significant (p = 6 × 10 −8 ) tendency for operon-encoded subunits to be lower in abundance than subunits from complexes encoded by different transcriptional units ( Figure 1 C).

In line with the elevated S-ASM activities in patients, we have found strong and highly significant correlations of S-ASM with these liver enzyme activities (Rho > 0.37 and p < 6 × 10 −8 for all three enzymes, Table 2 , Figure 3 ).

We found a highly significant increase in the deposition of collagen surrounding the ducts in the PAPP‐A transgenic females compared to the non‐transgenic females ( P = 6.013 × 10 −8 ) (Fig 2 F).

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 ).

In this cancer, a highly significant positive correlation was seen between the amount of nuclear FL BARD1 and nuclear p50 protein ( P = 6.14 × 10 −8 , Fisher’s exact test).

Interestingly, the OS genome-wide analysis identified 10 nearly significant variants (p value=6.3× 10 −8 ) on chromosome 2, in complete LD with each other ( figure 2 ).

Here, the difference was highly significant for pyramidal neurons (Fig. 2 c; p = 6.3 × 10 − 8 ).

For example, in the CI of QTL ID 42 (BTA5), detected for UD in HOL, we found a variant at 88,862,824 bp that also had, for the same trait, a significant effect in MON cows (− log 10 (P) = 7.4, results not shown) and an effect close to significance in MON bulls (− log 10 (P) = 7.2).

Also, the meta-analysis on these cohorts was highly significant ( P = 6.35 × 10 −8 for rs7021880).

In contrast, three borderline significant SNPs in the PLEKHA8 gene (rs11982167, rs11975522 and rs11773644) associated with NR3C1 gene expression ( P = 6.44 × 10 −8 ) showed weak evidence of association with Pred sensitivity ( P = 4.92 × 10 −2 ).

When the NAFLD phenotype was defined by ALT-threshold + dyslipidemia (ALT2DL, S6c Table in S1 File ), the association was highly significant in participants of EU ancestry (OR 1.05, P = 6.5x10 -8 ) as well as in the trans-ethnic meta-analysis (OR 1.05, P = 7 x 6.5x10 -9 ).

These filters resulted in a 10-fold reduction of the amount of data (from 32439 to 3243 CRUFTS or 6534 to 1593 non-overlapping regions) and increased the enrichment of known ncRNAs 2.17 fold, which is highly significant (p = 6.6e-8) (see Table 1 ).

These population differences are highly significant (Fisher’s exact test, p = 6.7e−8), and show that wS2 represents less low-level whisker kinematic information, or as we call it from now on, fine features.

A one‐way ANOVA revealed a highly significant difference in mean gall counts between genotypic classes ( F = 38.36, p = 6.73 × 10 −8 , R 2 = 0.78).

Ferroptosis Pathway Interestingly, KEGG pathway enrichment analysis demonstrated that ferroptosis (ID: hsa04216) ( Figure 4 A) was enriched at a highly significant level ( p -value = 6.79 × 10 −8 versus control) for the dual treatment (PRO plus CAP) than in other single treatments ( p -value = 0.05; PRO, p -value = 3.34 × 10 −6 for CAP versus control), which confirmed the synergistic interaction of the dual treatment that was obtained from the cytotoxicity study.

When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model ( P = 6.9 × 10 −8 ).

East Asian meta-analysis only found a borderline significant single-variant association (rs12530098 with the lowest p value; OR=1.10, p=6.9×10 –8 ).

The average codon volatility for the H class genes was 0.7609 + 0.001 while the S class had an average volatility of 0.7746 + 0.002 (Average + SE), a highly significant result (P = 6.9 × 10 -8 , double tailed t test).