# Shiny for Genetic Analysis Package (gap) Designs

This is an initial attempt to enable easy calculation/visualization of study designs from R/gap which benchmarked relevant publications and eventually the app can produce more generic results.

One can run the app with R/gap installation as follows,

    setwd(file.path(find.package("gap"),"shinygap"))
    library(shiny)
    runApp()

Alternatively, one can run the app from source using `gap/inst/shinygap`.

To set the default parameters, some compromises need to be made, e.g., Kp=[1e-5, 0.4], MAF=[1e-3, 0.8], alpha=[1e-8, 0.05], beta=[0.01, 0.4]. The slider inputs provide upper bounds of parameters.

## 1. Family-based study

This is a call to `fbsize()`.

## 2. Population-based study

This is a call to `pbsize()`.

## 3. Case-cohort study

This is a call to `ccsize()` whose `power` argument indcates power (TRUE) or sample size (FALSE) calculation.

## 4. Two-stage case-control design

This is a call to tscc().

# Appendix: Theory

## A. Family-based and population-based designs

See the R/gap package vignette jss or Zhao (2007).

## B. Case-cohort design

### B.1 Power

Following Cai and Zeng (2004), we have \[\Phi\left(Z_\alpha+\tilde{n}^\frac{1}{2}\theta\sqrt{\frac{p_1p_2p_D}{q+(1-q)p_D}}\right)\]

where \(\alpha\) is the significance level, \(\theta\) is the log-hazard ratio for two groups, \(p_j, j = 1, 2\), are the proportion of the two groups in the population (\(p_1 + p_2 = 1\)), \(\tilde{n}\) is the total number of subjects in the subcohort, \(p_D\) is the proportion of the failures in the full cohort, and \(q\) is the sampling fraction of the subcohort.

### B.2 Sample size

\[\tilde{n}=\frac{nBp_D}{n-B(1-p_D)}\] where \(B=\frac{Z_{1-\alpha}+Z_\beta}{\theta^2p_1p_2p_D}\) and \(n\) is the whole cohort size.

## C. Two-stage case-control design

In the notation of Skol et al. (2006),

\[P(|z_1|>C_1)P(|z_2|>C_2,sign(z_1)=sign(z_2))\] and \[P(|z_1|>C_1)P(|z_j|>C_j\,|\,|z_1|>C_1)\] for replication-based and joint analyses, respectively; where \(C_1\), \(C_2\), and \(C_j\) are threshoulds at stages 1, 2 replication and joint analysis, \(z_1 = z(p_1,p_2,n_1,n_2,\pi_{samples})\), \(\,\) \(z_2 = z(p_1,p_2,n_1,n_2,1-\pi_{samples})\), \(\,\) \(z_j = z_1 \sqrt{\pi_{samples}}+z_2\sqrt{1-\pi_{samples}}\).

# References

Cai, J., and D. Zeng. 2004. “Sample Size/Power Calculation for Case–Cohort Studies.” Journal Article. Biometrics 60 (4): 1015–24.
Skol, A. D., L. J. Scott, G. R. Abecasis, and M. Boehnke. 2006. “Joint Analysis Is More Efficient Than Replication-Based Analysis for Two-Stage Genome-Wide Association Studies.” Nat Genet 38 (2): 209–13.
Zhao, J. H. 2007. “Gap: Genetic Analysis Package.” Journal of Statistical Software 23 (8): 1–18. https://doi.org/10.18637/jss.v023.i08.