Table 3.
Statistical power analyses for actual multistage genome-wide association (GWA) studies and for hypothetical studies in which all available samples would be subjected upfront to genotyping in a GWA platform*
| Type of cancer | Sample, No. of case patients/No. of control subjects | Alpha level | Statistical power |
|||||
|
f = 10% |
f = 40% |
|||||||
| OR = 1.4 | OR = 1.2 | OR = 1.07 | OR = 1.4 | OR = 1.2 | OR = 1.07 | |||
| Breast cancer (42) | ||||||||
| Stage I | 390/364 | .052 | 0.33 | 0.13 | 0.06 | 0.65 | 0.25 | 0.08 |
| Stage II | 3990/3916 | 2 × 10−5 | 0.71 | 0.04 | 0 | 1 | 0.40 | 0 |
| Stage III† | 26 240/26 858 | 5 × 10−8 | 1 | 0.85 | 0 | 1 | 1 | 0.02 |
| Power of multistage design | 0.23 | 0 | 0 | 0.65 | 0.10 | 0 | ||
| Hypothetical achievable power‡ | 26 240/26 858 | 5 × 10−8 | 1 | 0.85 | 0.001 | 1 | 1 | 0.02 |
| Colorectal cancer (15) | ||||||||
| Stage I | 6780/6843 | 10−5 | 0.97 | 0.13 | 0 | 1 | 0.80 | 0.01 |
| Stage II§ | 20 186/20 855 | 5 × 10−8 | 1 | 0.60 | 0 | 1 | 1 | 0.02 |
| Power of multistage design | 0.97 | 0.08 | 0 | 1 | 0.80 | 0 | ||
| Hypothetical achievable power‡ | 20 186/20 855 | 5 × 10−8 | 1 | 0.60 | 0 | 1 | 1 | 0.02 |
The power of a statistical test represents the probability of rejecting a false null hypothesis (ie, finding an association when one truly exists) and depends on sample and effect size. The breast cancer GWA study (42) discovered six variants, of which one had an odds ratio (OR) = 1.20–1.40, five had OR = 1.07–1.20, and none had odds ratio less than 1.07 or greater than 1.40. The colorectal cancer meta-analysis of GWA studies (74) increased the total number of associations to 11, of which three had OR = 1.20–1.40, eight had OR = 1.07–1.20, and none had odds ratio less than 1.07 or greater than 1.40. f = minor allele frequency.
In this stage, all data from stage I and stage II and new replication data were combined; therefore, power calculations include all data.
Power achieved if all available samples from all stages could be evaluated in a GWA platform with discovery claimed at α = 5 × 10−8 level of significance.
In this stage, replication data were combined with data from stage I. Power calculations include all data. Calculations do not consider the possibility of better power if an enriched sampling design is used, for example, as in the colorectal cancer study (15]).