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Missing value imputation: As described above, we excluded variables with missing values more than 20%.
All markers with more than 20% missing values, more than 5% heterozygous genotypes, or minor allele frequencies less than 2.5% were excluded from the analysis.
For Stage 58 analysis, probes with a high proportion of missing values (more than two missing values across the biological replicates of each condition) were removed from the dataset.
From among this initial set, we dismissed three datasets that included treated samples, four datasets without control samples, five with too many missing values (more than 50% of missing values) and three generated with two-channel arrays.
Items with a relatively high number of missing values (more than 10%) must be avoided [ 24, 25] and might be left out of the basic questionnaire as they may not be applicable or relevant.
As a quality control, genes which presented too many missing values (more than 7 samples with no counts) and genes with a mean > 0.5 and SD > 0.2 across the samples were excluded, considering that genes presenting low counts are less reliable and genes which vary little provide limited information in a co-expression analysis [ 69].
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Markers with more than 20% missing values, or more than 5% heterozygous genotypes, or with minor allele frequency less than 2.5% were discarded [ 10].
When we compared the characteristics of the study participants who had at least one missing value in any area-level variable (n = 1,045) with those with available information for all area-level variables, individuals with missing values were more likely to be younger, economically active and more likely to have a higher household income, a higher education level, private health insurance.
Furthermore it has been suggested that missing values are more common when problems are present (thus, people are more willing to report the absence of problems) [ 35].
For each gene, CpG sites with missing values in more than 20% of the samples were removed, as well as samples with missing values in more than 20% of CpG sites.
Genes with missing values in more than 10% of samples were filtered out, and the remaining missing values were imputed using the average expression values within the group (case or control).
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