Table 1.
Simulations of Ascertainment Bias
| Simulation | Direct ascertainment window | Indirect ascertainment | Mean anticipation (years)a | Anticipation significantb | Mean additive heritabilitya | Heritability significantb | Mean year of birth/age of onset slopea | Slope significantb |
|---|---|---|---|---|---|---|---|---|
| 1 | 1989–2013 | None | 16.4 | 100% | 93% | 100% | −0.67 | 100% |
| 2 | 1950–2013 | None | 4.9 | 98% | 19% | 16% | −0.22 | 100% |
| 3 | 1880–2013 | None | 1.6 | 23% | 3% | 5% | −0.06 | 100% |
| 4 | 1989–2013 | Declining 5%/year | 10.7 | 100% | 59% | 83% | −0.55 | 100% |
| 5 | 1950–2013 | Declining 5%/year | 3.4 | 79% | 14% | 11% | −0.18 | 100% |
| 6 | 1880–2013 | Declining 5%/year | 1.4 | 18% | 3% | 6% | −0.05 | 98% |
| 7 | 1989–2013 | Declining 1%/year | 2.0 | 33% | 6% | 5% | −0.26 | 100% |
| 8 | 1950–2013 | Declining 1%/year | 0.9 | 12% | 4% | 5% | −0.12 | 100% |
| 9 | 1880–2013 | Declining 1%/year | 0.4 | 6% | 1% | 4% | −0.04 | 85% |
| 10 | 1989–2013 | Exhaustive | 0.2 | 5% | −1% | 5% | −0.20 | 99% |
Ascertaining only those individuals with disease onset within a historical window creates false signals of anticipation and heritability (Simulation 1). These false signals are reduced, but not eliminated, by expanding the ascertainment window (Simulations 2 and 3). Probabilistic retrospective ascertainment (see text) reduces these signals further (Simulations 4–9). Only when retrospective ascertainment is 100% exhaustive does anticipation become reliably nonsignificant (Simulation 10).
a
Averages from 1,000 simulations.
b
Percentage of 1,000 simulations in which this figure was statistically significant at p < 0.05.