Findings were prioritized based on significance thresholds and consistency across different analyses, and accounted for multiple testing and prior knowledge.
Because no critical value/threshold can be universally applied to all methods, results based on significance thresholds of different methods are not directly comparable.
These estimates may be inflated in comparison with the true effects, because of the "winner's curse" phenomenon (inflation of effects selected based on significance thresholds) (41, 42).
Such approaches often consider the genes selected based on significance thresholds, with the goal of predicting or finding associations with disease prognosis [ 25], adverse response to a chemical [ 26], disease pathogenesis [ 27], or identification of key genes in a pathway that may serve as biomarkers [ 28].
Signal was then thresholded based on significance.
In rare cases, two SNPs which are individually not genome-wide significant may show a significant interaction effect, but they may be excluded from the analysis based on the significance threshold.
However, this approach clearly introduces a dichotomous decision, since it is based on a significance threshold.
A total 15 single nucleotide polymorphisms (SNPs) were selected from the Immunochip study based on a significance threshold of p<1×10−4.
VBM analyses are based on statistical significance thresholding, where thresholds are estimated using random field theory to correct for multiple dependent comparisons [Worsley et al., 1996].
For this analysis the loci, although fully linked, were tested independently because combining multiple sites, each mutating independently, into a synthetic genotype may introduce a bias on significance thresholds, which are based on independent loci, and not a linear combination of repeat lengths of multiple loci.
