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The Kruskal-Wallis test revealed statistically significant differences among groups (p = 0.029), also confirmed by a multiple test adjusting procedure based on the rank-means paired differences (p = 0.018) (Table 2). Figure 1 Cephalalgiaphobia and frequency of migraine.

A multiple test adjusting procedure, based on the rank-means paired differences, has been applied if the overall test was significant at the 0.05 level [32].

A multiple test adjusting procedure, based on the rank-means paired differences, showed statistical significance both in patients who worsened vs. those who remained on the same level (p = 0.011) but also vs. those who improved (p = 0.012).

A multiple test adjusting procedure, based on the rank-means paired differences, showed that this statistical significance was attributable to the difference between 2nd vs. 1st group (p < 0.001) and 3rd vs. 1st (p < 0.001) but not to 3rd vs. 2nd group (Table 2).

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Additionally, we probed for canonical pathways enrichment using the Ingenuity Pathway Analysis (IPA) tools and calculated the multiple test adjusted P-value for each pathway according to the fit of user's data to IPA database.

The multiple testing adjusting method for P-values is the Benjamini and Hochberg algorithm.

Only 60 CpGs revealed significant association upon adjustment for multiple testing (adjusted P < 0.05; Fig.  1b).

For drug screen data, probesets were selected for further analysis if the fold change was greater than 2 and multiple testing adjusted p-value using Benjamini and Hochberg procedure (BH-adjusted p-value) was less than 0.05 [37].

Multiple testing adjusted significant thresholds to the 5%-level were determined by Bonferroni-adjustment or by permutation test (50 000 permutations, to account for correlations between cognitive phenotypes).

These tests were not considered significant after applying Bonferroni corrections for multiple tests (adjusted significance level: α' = 0.009).

Probes were selected for further analysis if the fold-induction was greater than 2 and multiple testing adjusted the p-value to less than 0.05 using Benjamini and Hochberg procedure (BH-adjusted p-value) [28].

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