MA-SNP--A new genotype calling method for oligonucleotide SNP arrays modeling the batch effect with a normal mixture...

Genome-wide association studies hold great promise in identifying disease-susceptibility variants and understanding the genetic etiology of complex diseases. Microarray technology enables the genotyping of millions of single nucleotide polymorphisms. Many factors in microarray studies, such as probe selection, sample quality, and experimental process and batch, have substantial effect on the genotype calling accuracy, which is crucial for downstream analyses. Failure to account for the variability of these sources may lead to inaccurate genotype calls and false positive and false negative findings. In this study, we develop a SNP-specific genotype calling algorithm based on the probe intensity composite representation (PICR) model, while using a normal mixture model to account for the variability of batch effect on the genotype calls. We demonstrate our method with SNP array data in a few studies, including the HapMap project, the coronary heart disease and the UK Blood Service Control studies by the Wellcome Trust Case-Control Consortium, and a methylation profiling study. Our single array based approach outperforms PICR and is comparable to the best multi-array genotype calling methods.