We performed high-throughput genome-wide SNP genotyping using the InfiniumII HumanHap550 BeadChip (Illumina) at the Center for Applied Genomics at the CHOP. The genotype data content together with the intensity data from the genotyping array provided high confidence for the CNV calls. A simultaneous analysis of intensity data and genotype data in the same experimental setting established a highly accurate definition for normal diploid states and any deviation thereof. To call CNVs, we used PennCNV and QuantiSNP. PennCNV combines multiple sources of information, including LRR and BAF, SNP spacing, trained Hidden Markov Models and the population frequency of the B allele to generate CNV calls. The replication case and control cohorts performed genome-wide SNP genotyping using the Perlegen 600K, Illumina 1M and Affymetrix 5.0 arrays. Raw X and Y values were log10 normalized and clustered to establish the BAF and LRR values using the PennCNV-Affy protocol (Online Methods and Supplementary Table 12).
