differences between “disease” and “control” samples, as noted above, 2) uneven distribution of noise in some assays, so that SNPs with the largest variance might be identified rather than the SNPs whose allelic frequencies truly differ between disease and control individuals, 3) stochastic, chance differences between disease and control samples (at least some of these are highly likely in any single study that uses so many repeated comparisons) and 4) sampling issues so that genetics related to the ways in which the samples are ascertained and obtained (eg features such as differential willingness to consent) is identified rather than true disease/control differences. Many of these concerns become more prominent as hundreds of thousands or millions of repeated comparisons are made using single sample sets. Many of these concerns may be more acute as attempts to rapidly assemble samples with larger and larger “n” drive investigators to include subsamples that may well contribute occult heterogeneities to overall disease and/or control samples (see below).
