penetrance: Penetrance function and confidence intervals

In FamEvent: Family Age-at-Onset Data Simulation and Penetrance Estimation

Penetrance function and confidence intervals

Description

Estimates the cumulative disease risks (penetrances) and confidence intervals at given age(s) based on the fitted penetrance model.

Usage

  penetrance(fit, fixed, age, CI = TRUE, MC = 100)

Arguments

fit	An object class of 'penmodel', a fitted model by penmodel or penmodelEM functions.
fixed	Vector of fixed values of the covariates used for penetrance calculation.
age	Vector of ages used for penetrance calculation.
CI	Logical; if TRUE, the 95% confidence interval will be obtained using a Monte-Carlo method, otherwise no confidence interval will be provided. Default is TRUE.
MC	Number of simulated samples used to calculate confidence intervals with a Monte-Carlo method. If MC=0, no confidence intervals will be calculated. Default value is 100.

Details

The penetrance function is defined as the probability of developing a disease by age t given fixed values of covariates x,

P(T < t | x) = 1 - S(t; x),

where t is greater than the minimum age t₀ and S(t; x) is the survival distribution based on a proportional hazards model with a specified baseline hazard distribution.

The proportional hazards model is specified as: h(t|x) = h₀(t) exp(β*x), where h₀(t) is the baseline hazards function, x is the vector of covariates and β is the vector of corresponding regression coefficients.

Calculations of standard errors of the penetrance estimates and 95% confidence intervals (CIs) for the penetrance at a given age are based on Monte-Carlo simulations of the estimated penetrance model.

A multivariate normal distribution is assumed for the parameter estimates, and MC = n sets of the parameters are generated from the multivariate normal distribution with the parameter estimates and their variance-covariance matrix. For each simulated set, a penetrance estimate is calculated at a given age by substituting the simulated parameters into the penetrance function.

The standard error of the penetrance estimate at a given age is calculated by the standard deviation of penetrance estimates obtained from n simulations.

The 95% CI for the penetrance at a given age is calculated using the 2.5th and 97.5th percentiles of the penetrance estimates obtained from n simulations.

Value

Returns the following values:

age	Ages at which the penetrances are calculated.
penetrance	Penetrance estimates at given ages.
lower	Lower limit of the 95% confidence interval; simulation-based 2.5th percentile of the penetrance estimates.
upper	Upper limit of the 95% confidence interval; simulation-based 97.5th percentile of the penetrance estimates.
se	Simulation-based standard errors of the penetrance estimates.

Author(s)

Yun-Hee Choi

See Also

simfam, penmodel, penmodelEM

Examples

  set.seed(4321)
  fam <- simfam(N.fam = 100, design = "pop+", base.dist = "Weibull", allelefreq = 0.02, 
         base.parms = c(0.01,3), vbeta = c(-1.13, 2.35))
	
  fit <- penmodel(Surv(time, status) ~ gender +  mgene, cluster = "famID", 
         parms = c(0.01, 3, -1.13, 2.35),  data = fam, base.dist = "Weibull", design = "pop+")
 
 # Compute penetrance estimates for male carriers at age 40, 50, 60, and 70 and
 # their 95% CIs based on 100 Monte Carlo simulations.
 
 penetrance(fit, fixed = c(1,1), age = c(40, 50, 60, 70), CI = TRUE, MC = 100)

FamEvent documentation built on Nov. 17, 2022, 5:06 p.m.