Large CNVs can be split by CNV calling algorithms; as is customary to overcome this issue, adjacent CNV calls were merged.10 We merged adjacent CNV calls larger than 200 kb that occurred in a single individual where the gap was less than 50% of the entire length of the newly merged CNV. The log R ratio and B allele frequency of SNPs spanning all CNVs generated from merging adjacent calls were manually inspected before acceptance. At loci where the log R ratio and B allele frequency did not support the presence of a split, adjacent CNVs were not merged (eg, heterozygote genotype calls between adjacent hemizygous CNVs). In keeping with previous studies,10 we excluded CNVs for which more than 50% of their length spanned known gaps of at least 200 kb in the SNP array, genomic segments containing more than 14 CNVs (ie, >1% frequency) in the combined patients and controls, known segmental duplications present in the March, 2006 human reference sequence (National Center for Biotechnology Information reference build 36.1, hg18), or known common CNVs defined by the Genome Structural Variation Consortium.
