Table 1.

Average Estimated Inflation in Estimates of Variation Explained for Several Case-Control Ascertainment Schemes in WTCCC Control Data

Ascertainment scheme	A (80% and 20%)a	B (75% and 30%)b	Null Model (50% and 50%)c
Average estimated variance explained	8.1%	3.9%	2.1%
Standard error	0.6%	0.4%	0.3%

We computed the mean estimated variance of phenotype explained for 100 realizations of each ascertainment scheme. The estimated percentage of variance explained is constrained to be nonnegative, so even the null model gives a small average estimated variance explained, however the difference between the null results and the results from schemes A and B is statistically significant. The ascertainment in scheme B is similar to ascertainment in the WTCCC Bipolar study in which 72% of Welsh were cases, whereas 34% of English were cases. All results were generated with 20 PCs, a 0.025 cut-off on relatedness and no adjustment for incomplete LD, and are reported on the liability scale with 1% prevalence. We note that although scheme B is designed to give similar regional proportions to those in the WTCCC Bipolar data, the regional information for the WTCCC data is crude and does not fully capture the population structure in the data. Thus, we are not able to fully model the geographical (and possibly socio-economic) ascertainment differences between the cases and controls, which limits the effect sizes that we can observe in our simulations.

^aAscertainment scheme A has 80% of Welsh and Scots designated as cases and 20% of English designated as cases.

^bAscertainment scheme B has 75% of Welsh and Scots designated as cases and 30% of English as designated as cases.

^cThe null scheme has equal ascertainment of cases and controls across all subpopulations (50% cases). A scheme with 30% as cases in all subpopulations gave identical results (data not shown).