For the two initial scans, PLCOca-PLCOco and NHSca-NHSco, no significant difference (after multiple comparison adjustments) was observed between cases and controls with respect to the distribution on each of the top 5 PC directions (Table 3). Thus, a strong confounding effect by PS in either study is not to be expected, even though PC directions with significantly large genetic variation are evident in these studies. For the two reconstructed studies with external controls, i.e., PLCOca-NHSco and NHSca-PLCOco, cases and external controls display significantly different distributions along the first two PC directions. There is also a third direction (the 4th PC direction in PLCOca-NHSco, and the 3rd PC direction in NHSca-PLCOco) along which cases and external controls differ, although to a lesser extent. Thus, compared with the two studies with internal controls, these findings suggest that the confounding effects by PS are accentuated when controls are culled from an independent study.
