Gene copy number analysis for family data using semiparametric copula model

Gene copy number changes are common characteristics of many genetic disorders. A new technology, array comparative genomic hybridization (a-CGH), is widely used today to screen for gains and losses in cancers and other genetic diseases with high resolution at the genome level or for specific chromosomal region. Statistical methods for analyzing such a-CGH data have been developed. However, most of the existing methods are for unrelated individual data and the results from them provide explanation for horizontal variations in copy number changes. It is potentially meaningful to develop a statistical method that will allow for the analysis of family data to investigate the vertical kinship effects as well. Here we consider a semiparametric model based on clustering method in which the marginal distributions are estimated nonparametrically, and the familial dependence structure is modeled by copula. The model is illustrated and evaluated using simulated data. Our results show that the proposed method is more robust than the commonly used multivariate normal model. Finally, we demonstrated the utility of our method using a real dataset.