Family-based association test using normal approximation to gene dropping null distribution

Abstract

We derive the analytical mean and variance of the score test statistic in gene-dropping simulations and approximate the null distribution of the test statistic by a normal distribution. We provide insights into the gene-dropping test by decomposing the test statistic into two components: the first component provides information about linkage, and the second component provides information about fine mapping under the linkage peak. We demonstrate our theoretical findings by applying the gene-dropping test to the simulated data set from Genetic Analysis Workshop 18 and comparing its performance with existing population and family-based association tests.