Including rs74653330 (p.Ala481Thr), a missense lead variant in OCA2 , a total of 12 independent nonsynonymous variants associated with skin color traits were identified in the GWAS (Supplementary Data 5 ): 1 in a previously unreported locus, 9 in previously reported loci, and 2 in nominally significant loci (top variants of 2 loci did not pass the genome-wide significance level, P < 5.0 × 10 −8 ).
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Whilst both models indicated a highly significant relation between heritability and hierarchical level ( F -tests; linear: R 2 = 0.49, F 1,44 = 43, p = 5.1 × 10 −8 ; quadratic: R 2 = 0.67, F 2,43 = 44.1, p = 3.8 × 10 −11 ), the quadratic model fitted the data better than the linear model ( F -test, F 1,43 = 23.3, p = 1.8 × 10 −5 ) because heritability increased significantly from V1 to V3 ( t -test, t 8 = 2.38, p = 0.04).
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 ).
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).
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.
3c ) and a less strong yet still highly significant directional effect of intelligence on BV ( b xy = 0.139, SE = 0.026, P = 7.34 × 10 −8 ; Fig. 3d ), suggesting a bidirectional association between these phenotypes, in line with the previous reports 53 .
The clusters are highly significant in predicting survival (likelihood ratio = 37.0; p = 7.6×10 −8 ), also accounting for clinical and histopathological information (age, stage and cancer type; Methods), showing that considering the mutation data and their interactions provides a more complete and informative picture of tumours and their progression.
Separate analysis of the deletions and duplications showed a highly significant effect from the deletions ( β = 2.56 cm, P = 8.2 × 10 −8 ).
This positive coupling of both treatments was highly significant in a χ 2 -test of homogeneity ( χ 2 =29.6, degree of freedom=1, P <10 −7 ; Supplementary Table 5 ).
Similarly, while only a marginal association was seen with parasite density for ABO ( p = 0.01), a highly significant association was seen with plasma Pf HRP2 concentration ( p = 10 −7 , Fig. 2 ).
3c ), the interaction was not significant ( F (1, 33)<1, P =0.37), but there was a highly significant main effect of saliency ( F (1, 33)=62.34, P =1.0e−07), and a significant main effect of saccade-goal ( F (1, 33)=12.58, P =0.0011).
Interestingly, mass spectrometry analysis revealed that differentiation of Nsd1 -expressing Nsd1 −/− erythroblasts was associated with a highly significant reduction (logFC = −1.96; p < 1.08 × 10 −7 ) of the transcriptional repressor protein SKI previously proposed to interact with and inhibit GATA1 activation, most likely in cooperation with the nuclear co-repressor (NCoR) complex (Fig. 8g, h , Supplementary Fig. 6d ) 43 , 44 .
In complete contrast, no bias ( p = 0.92, two-sided binomial test) is seen for all multiple-SNP tracts combined, and the difference relative to single-SNP tracts is highly significant ( p = 1.1 × 10 −7 , Fisher’s exact test).
More broadly, mRNAs putatively mis-spliced in p62 −/− brains included a highly significant proportion of mRNAs (97 of 862, p = 1.57 × 10 −7 ) that bound to FUS and were mis-spliced in FUS-deficient brains 41 (Fig. 5m , Supplementary Fig. 5p ).
We found marginally non-significant support for two-rate models for binary (i.e., presence or absence) conjugation ( P = 0.059; Likelihood Ratio Test) and highly significant support for two-rate models for SAM ( P = 1.58e-07; Supplementary Table 4 ).
Meta-analysis of SNPs common to all four GWAS ( N = 6661818 and N = 6496414 for all AML and cytogenetically normal AML, respectively) also revealed additional borderline significant susceptibility loci at 1p31.1 (rs10789158, CACHD1 , P = 2.25 × 10 −7 ) for all AML and at 7q33 (rs17773014, AKR1B1 , P = 4.09 × 10 −7 ) for cytogenetically normal AML, both with consistent direction and magnitude of effect across all four studies (Figs. 1 and 2 ).
On an ordinary scale progressing from control to sepsis to septic shock, Chymase levels displayed a strong and highly significant positive correlation (Spearman’s coefficient r s = 0,54, p = 3×10 -7 ), Ang 1 a significant negative correlation (r s = -0,27, p = 0,014), and Ang2 a weak but significant positive correlation (r s =0,23, p = 0,053) with sepsis severity (Supplemental Fig. 4 ).
These two highly significant SNPs (rs10842383 near LINC00477 , P =3.45 × 10 −7 and rs2680344 in HCN4 , P =4.34 × 10 −7 ( Supplementary Table 12 ) had large opposite effects on atrial fibrillation, while both decreased HRV.
In contrast, class II genes showed a significant trend for downregulation relative to ESCs (Kruskal–Wallis test, p = 4 × 10 −7 ).
Purifying selection is highly significant for all models ( P ≤ 5.0 × 10 −7 , Z-tests) (Supplementary Fig. 1 ).
Regression analysis of PC1 scores confirmed that age had no significant impact on sample distribution (coefficient = 0.28; p = 0.43), whereas group was the dominant determinant of separation, with a strong and highly significant coefficient of 81.47 ( p = 7.86 × 10−7) (Supplementary Fig. 2E ).
Overall, the reconciled tree contained 44 duplication and 28 deletion events, of which only one duplication but 15 deletions were assigned to socially parasitic lineages, a highly significant difference ( Χ 2 = 24.18, p = 9e−07, df = 1).
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
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 ).
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.