Our main purpose in using two control groups was to assess possible bias in ascertaining control samples. In addition, noting that DNA sample processing differed between these groups, comparison of control groups also provides a check for effects of differential genotyping errors as a result of differences in DNA collection and preparation. Figure 1a shows the results of 1-d.f. Mantel-extension tests5 for differences in allele frequencies of SNPs between subjects from the 58BC and UKBS collections, stratified by 12 broad regions of Great Britain (see Supplementary Table 5 and Supplementary Fig. 4 for region definitions). The associated quantile-quantile plot (see Methods for background) in Fig. 1b shows good agreement with the null distribution (similar results are obtained for tests that do not stratify by geography, data not shown). The fact that we see few significant differences between these two control groups despite the fact that they differ in population groups sampled, DNA processing, and age, indicates that there would be little bias due to use of either sample as a control group for any of the case series, and justifies our combining of the two control groups to form a single group of 3,000 subjects for our main analyses.
