Quality control for samples, the procedures for CNV calling, and quality control for the CNV calls are described in the online data supplement. The genome-wide burden of rare CNVs was assessed according to either the number of rare CNVs per sample or the average rare CNV size per sample. Gene-centric burden analysis was performed by limiting the analysis to rare CNVs that overlapped with the list of genes (defined according to +/– 50 kb of the largest transcript) present in National Center for Biotechnology Information Build 36.1-hg18 (http://pngu.mgh.harvard.edu/∼purcell/plink/res.shtml#glist). In accordance with other studies, the significance of the burden comparisons was assessed via permutation (10,000 permutations, one-sided test) using PLINK (http://pngu.mgh.harvard.edu/∼purcell/plink). Analyses were performed for all large, rare CNVs as well as by stratification according to CNV type (deletion or duplication) and size (>100 kb or >500 kb). Differences in the rates at which CNVs were called in males or females were assessed separately in case and comparison subjects using PLINK, with significance assessed via permutation (10,000 permutations, two-sided test).
