Excerpts

1c, d ) is highly significant ( P = 3.06 × 10 −33 ) and cannot be explained by a random process of microbial recruitment from the same starting soil community.

We found a highly significant overlap between them (265 pairs, p = 1.4E−32, Fisher exact test, Fig. 6c ).

Logistic regression models predicting each treatment from diagnosis yielded highly significant associations (BH-adjusted p < 1 × 10 −30 ; Supplementary Data 5 ), indicating that diagnosis and treatment are not independently distributed.

Across cell types and haplotypes, we found a positive and highly significant correlation (Pearson correlation; cell type: p = 2.36 × 10 −30 , haplotype p = 6.76 × 10 −4 , Fig. 7d ) between gene expression fold change and chromatin loop fold change, and between H3K27ac fold change and loop fold change (Pearson correlation; cell type: p = 6.6 × 10 −211 ; haplotype: p = 4.63 × 10 −5 , Fig. 7e ).

We found a highly significant replication (mean R 2 = 0.07; P = 1.5 × 10 −29 ), explaining 41% of in-sample cross-validation R 2 (Supplementary Figure 3 ), which is consistent with previous out-of-sample estimates 24 , 25 .

11C ) and show a highly significant correlation ( R = 0.67, p < 5e−29, for diverse environments.

When we performed a gene-set enrichment analysis of these 1,341 genes using the Database for Annotation, Visualization and Integrated Discovery 20 , we found highly significant enrichment of ‘SP_PIR_KEYWORDS: alternative splicing' (Benjamini-corrected P =8.6 × 10 −29 ) and ‘UP_SEQ_FEATURE: splice variants' (Benjamini-corrected P =1.1 × 10 28 ), which denote genes with known splicing isoforms ( Supplementary Data 2 ).

In addition, we identified highly significant missense variants (<5 × 10 −15 ) within the FLG gene (rs558269137, beta = −0.222, p = 1.96 × 10 −27 ) and the KRT1 gene (rs14024, beta = −0.030, p = 3.95 × 10 −15 ).

The samples clustered into two distinct and well-separated classes, and evaluation of the model showed that it was highly significant ( p = 2.3E −27 permutations p = <0.001).

We detected approximately 15.000 transcripts in the ventricles and surprisingly, within the TAD only Scn5a expression was highly significant downregulated ( P = 3.75e-27) in RE6-9 +/− mice (Fig. 4c–f ).

The average difference in TraP scores between the groups is highly significant (0.62 vs. 0.078, pathogenic versus benign variants, respectively, MW-test, P -value = 7.1 × 10 −27 ).

Gene Ontology (GO) analysis of the upregulated genes by miR-182 deficiency during RANKL-induced osteoclastogenesis revealed highly significant activation of genes involved in defense response, in particular interferon-β response ( p < 10 −25 , Fig. 4b ).

Moreover, an independent RF classification model applied to the primary tumors using TCGA DNAm data revealed a highly significant overlap in the top 100 most predictive genomic regions between the BM and the primary tumor classifiers (Hypergeometric test; P -value < 2.8e−23).

Previous reports have implicated deleterious coding variants in IFIH1 , the third member of the RLR family, as conferring protection against psoriasis 8 , 71 and psoriatic arthritis 72 ; the protective IFIH1 variants rs35667974 and rs1990760 are both highly significant in the current meta-analysis ( P = 5.0 × 10 −23 and 7.0 × 10 −50 , respectively) but not prioritised in credible sets due to insufficient effective sample size and the presence of a more strongly associated intronic variant (rs2111485), respectively.

The DML overlap between the two cohorts was highly significant ( p = 1.71 × 10 −22 , 8.17 × 10 −33 and 3.13 × 10 −44 in B cell, memory T cell and Naïve T cells, respectively, by hypergeometric tests).

Analyzing the same brain regions from another group of mice using our custom array platform revealed another highly significant CpG to be hypomethylated in the Q175 group (probe cg12389415 on the custom array, mouse chr5:34795955) also within the Htt locus (meta-analysis p = 3.2 × 10 −22 ; Supplementary Fig. 25 ).

Because adipocytes are the predominant stromal cell type in mammary tissue, we also performed follow-up analyses using the S-PrediXcan subcutaneous fat model and discovered a highly significant ( p value=2.1 × 10 −20 ) association of ZNF703 with increased breast cancer risk in the four-fold larger BCAC/DRIVE dataset, consistent with the MiXcan stromal cell results in the DRIVE data only.

There were highly significant differences in regional grey matter volumes, particularly of mid- and hindbrain structures, such as cerebellum (beta = −9.91E-04, T = −9.26, P = 2.25E-20), pons (beta = −5.63E-04, T = −6.23, P = 4.95E-10) and midbrain (beta = −4.00E-04, T = −5.15, P = 2.67E-07) in gout and high urate (Fig. 2 ).

The effects of the PRSs for BPH/LUTS and prostate cancer on PSA levels are largely independent since, in a joint analysis the effect of both remained highly significant, i.e. 8.6% increase ( P = 3.0 × 10 −20 ) and 13.3% increase ( P = 4.1 × 10 −43 ), respectively (Table 2b ).

There was a notable trend toward lengthening of the 3’UTR in cancer cells ( P = 5.59 × 10 −20 ), with COL1A2 emerging once more as the most prominent finding ( P corr =7.48 × 10 −47 , 61% change) (Figs. 3b, c and 4f ).

This analysis revealed a class of highly significant motifs correlated with open chromatin that were common to both host and graft cells and a variety of other myeloid cells ( p < 10e−20) such as CTCF, SPI1, and Runx binding motifs (Supplementary Fig. 7b ).

Lastly, for TGA1, a well-studied TF in N signaling 26 – 28 , we observed a large and highly significant overlap (600 genes, p value = 1.78E−19, Fisher’s exact test) of direct regulated targets identified in root cells using the TARGET system, compared to DE genes resulting from TGA1 overexpression in roots of whole plants (Supplementary Data 4 and Supplementary Fig. 7 ) (see Methods).

Association results between TC PRS and TC response to statins were highly significant ( p -value < 2.51e−19) and directionally concordant with LDL-C results.

Further, when smaller geographical areas were considered (France is divided into 96 administrative units, called departments), these correlations remained highly significant (e.g., admissions to CCRUs: R smell = 0.76, p < 5 × 10 −19 ) (Fig. 1c ).

Despite the low abundance of Mic.15, the association signal of PPP1R37 was highly significant ( p -value = 2.9 × 10 −18 ), suggesting that AD-associated variants may regulate PPP1R37 specifically in the inflammatory microglial subtype.