Several limitations should be noted, including the effects of multiple comparisons; significant results in the subgroup analyses in particular could be because of chance alone.
The retrospective, post hoc analyses presented here are limited by small subgroups and lack of correction for multiple comparisons; significant results should be viewed as exploratory and should be confirmed in future studies.
After considering a multiple testing correction (−log10 pFDR >3), no significant results were found for single-locus association tests.
The maximum number of samples was chosen to ensure the possibility of significant results after multiple testing correction.
A summary of significant results from multiple logistic and linear regression analyses of outcomes of consultants' communications is shown in Table 4 >.
In an effort to minimize the risk of falsely identifying significant results with multiple comparisons, all variables were specified and judged a priori to be clinically sound.
As a result of the selective reporting of significant results from multiple analyses and publication bias, the extent of type I error in the published literature may be great [ 11, 14, 21, 23, 26, 28, 30, 40, 41].
We therefore imposed a ceiling on the maximum number of samples for sequential MC, set to 50 000 to ensure the possibility of significant results after multiple testing correction (indeed, using a maximum of 10 000 samples for sequential MC missed all significant results when asking about overrepresentation of H3K4me2 downstream in genes).
It is quite reasonable that zonulin may in turn have a regulation on p38 MAPK pathway or a double regulation between P38 MAPK and zonulin, given similar signaling of the zonulin prokariotic analogue Zot [ 39],further basic studies may be needed Assessment of numerous outcome gives rise to a multiple comparison issue, especially marginally significant results, which require cautious analyse.
To cope with the multiplicity effect, that is, the chances of getting an increased number of significant results due to multiple tests, we adjusted the values as described in [34].
