Background: Copy number variations (CNVs) may play an important role in disease risk by altering dosage of genes and other regulatory elements, which may have functional and, ultimately, phenotypic consequences. Therefore, determining whether a CNV is associated or not with a given disease might be relevant in understanding the genesis and progression of human diseases. Current stage technology give CNV probe signal from which copy number status is inferred. Incorporating uncertainty of CNV calling in the statistical analysis is therefore a highly important aspect. In this paper, we present a framework for assessing association between CNVs and disease in case-control studies where uncertainty is taken into account. We also indicate how to use the model to analyze continuous traits and adjust for confounding covariates.
Results: Through simulation studies, we show that our method outperforms other simple methods based on inferring the underlying CNV and assessing association using regular tests that do not propagate call uncertainty. We apply the method to a real data set in a controlled MLPA experiment showing good results. The methodology is also extended to illustrate how to analyze aCGH data.
Conclusion: We demonstrate that our method is robust and achieves maximal theoretical power since it accommodates uncertainty when copy number status are inferred. We have made R functions freely available.