Excerpts

Multivariate linear regression analysis detected a highly significant association between blood-based DNAm-age acceleration and ALS age of onset (adjusted p value = 2.2E-16, B = − 1.29, R 2 = 0.33, n = 249) (Supplementary methods, Fig. 1 a), suggesting that for every 5-year increase in DNAm-age acceleration there is a 6.4-year earlier onset.

Consistent with previous reports ( Vetter et al., 2004 ), there were highly significant differences in both impedance magnitude ( Figure 5B : χ 2 = 311.86, p < 2.2 × 10 −16 , df = 8; Kruskal–Wallis test) and phase angle ( Figure 5C : χ 2 = 164.72, p < 2.2 × 10 –16 , df = 8; Kruskal–Wallis test) during the first WPI.

The difference in heteroplasmy between sexes was highly significant (129/0 males and 570/32 females,Chi-Square test, p- value < 2.2 × 10 −16 ) and corroborates results from a previous study 24 .

A chi-squared test revealed a highly significant difference in the distribution of genes across score ranges among the three categories (χ2 = 519.5, df = 18, p < 2.2 × 10−16), indicating that gene distributions differed substantially between them.

All four of the tested trait correlations were highly significant when evaluating the spatial relationships (both current and future) between predicted trait distributions (Figure 6 ; p = 2.2e −16 ).

There was, however, a highly significant correlation between change in TE score and GC content (Pearson’s correlation value of −0.1337, p-value<2.2e −16 ) ( Figure 1I ).

Although circRNA expression shows a clear trend for both positive (β = 1.121, P < 2.2 × 10 −16 ) and negative (β = −1.015, P < 2.2 × 10 −16 ) β values (effect size), there is no such trend in the mRNA expression (β = 0.0294, P = 0.8654; and β = −0.0339, P = 0.8639 for positive and negative β values, respectively).

The correlation of the concentrations determined by 1 H-NMR and by quantitative methods were highly significant for both the samples of ccDMEM (Pearson: r = 0.99, p = 2.20 * 10 −16 ) and of vcDMEM (Pearson: r = 0.91, p = 2.84 * 10 −6 ).

It is evident from the data that genome size influences the frequency of microsatellites, supported by a highly significant positive correlation between genome sizes and frequency of microsatellites ( R 2 = 0.53 and P -value = 2.2e –16 ) ( Fig. 2D ).

The complete monotherapy rates for SGAs without other psychotropic medications in 2001, 2006, 2011, 2016 and 2021 were only 0.7%, 2.7%, 3.5%, 5.0% and 6.3%, respectively ( Table 1 ), with an increasing trend (χ2 = 37.6, df = 1, p = 9.0×10 −10 ). The rates of FGA use in 2001, 2006, 2011, 2016 and 2021 were 85.6%, 77.5%, 70.7%, 65.1% and 54.7%, respectively ( Table 1 and Figure 1A ), with a decreasing trend (χ2 = 190.2, df = 1, p < 2.2×10 −16 ).

Although the results of the test for direction of change in expression of X-linked transcripts in CDX males compared to Control males was highly significant (χ 2 = 82.7517, df = 3, P -value <2.2*10 −16 ), there was no evidence that these transcripts had feminized expression levels in CDX males ( Table 2 ).

Comparing the two sets of genes, we observed a highly significant overlap of 193 genes whose expression was altered by either IL-1β treatment and IL-1R8 deficiency (Fischer’s exact test; P value = 2.2e-16; Pearson correlation coefficient = 0.95; 61.7% downregulated and 38.3% upregulated, Supplementary file 3 ).

Their overlap of 306 genes is highly significant (Fisher’s exact test p-value < 2.2e-16).

The correlation between ω A MK and DoS was strong and highly significant (ρ = 0.964, P -value < 2.2E-16, n = 10,631, supplementary fig.

1c ), which exhibited highly significant hypomethylation ( P < 2.2e-16; Fig. 1d ).

Strikingly, as in human cells, we found a highly significant correlation between 8-oxodG and γH2AX signals within the mouse genes (Pearson correlation test, r = 0.9; P < 2.2e–16) (Figure 4F ).

However, these correlations were still highly significant ( P values < 2.2e-16 in both Pearson and Spearman correlation tests).

In the wild fish, as well as in the Nadia strain, the chi-square P values are highly significant ( P < 2.2e-16), and one sees a clear bias in favor of G/C to A/T for the low-frequency class alleles and a bias in favor of A/T to G/C for alleles occurring at high frequencies, both expected under gBGC ( Glemin et al. 2015 ).

R ESULTS Analysis of flexural strength values for all the study groups by two-way ANOVA indicated a very highly significant difference between the means of all main groups ( F = 14056.27, P < 2.2E-16) and between the means of subgroups ( F = 94.41, P < 2.2E-16) [ Table 1 ].

Our results indicated that 48.1% ( n = 11,422, P < 0.05) of the examined drift-CpGs exhibited a nominally significant difference (OR = 5.0, Fisher's test, P < 2.2 × 10 −16 ) between these two time points.

The overestimates were highly significant (1-tailed paired t -test, t = 26.60, df = 519, p < 2.2 −16 ).

Based on the comparison of intact to degraded cartilage, the log-fold-changes in RNA expression and the differences in mean promoter region methylation values demonstrated a small but highly significant correlation (Pearson’s r = −0.08, p < 2.2 × 10 −16 , Fig. 2b , Supplementary Table S7 ).

We observed a very weak but highly significant correlation in synonymous heterozygosity between species (Pearson’s r = 0.14, p<2.2e-16), consistent with some degree of conservation for genic parameters of mutation rates and/or selection at Drosophila synonymous sites [ 58 , 70 – 74 ].

The correlation between the inbreeding coefficients and F ROH were also highly significant (F I: r = 0.71, P = 2.20 × 10 −16 ; F II: r = 0.72, P = 2.20 × 10 −16 ; F III: r = 0.83, P = 2.20 × 10 −16 ).

We observe a highly significant 3-way MT × N × E interaction ( P << 2.2 × 10 −16 ) ( Table 1 ) and highly significant MT × N epistasis within each of the 6 conditions ( Table 2 ).