The CNV frequency between cases and controls was evaluated at each SNP using a Fisher’s exact test. We only considered loci that were nominally significant between cases and controls (P < 0.05) when cases in the CHOP discovery cohort had the same variation, which was replicated in the IMAGE, PUWMa or IMAGE II studies, or loci that were not observed in any of the control subjects and were validated using an independent method. We reported statistical local minimums to narrow the association in reference to a region of nominal significance, including SNPs residing within 1 Mb of each other (Supplementary Fig. 10). The resulting nominally significant CNVRs were excluded if they met any of the following criteria: (i) residing on telomere- or centromere-proximal cytobands; (ii) located in a ‘peninsula’ of common CNVs arising from variation in boundary truncation of CNV calling (Supplementary Fig. 11); (iii) genomic regions with extremes of GC content, which produces hybridization bias; or (iv) samples contributing to multiple CNVRs. See ParseCNV for details (see URLs). We statistically adjusted for the relatedness of cases using permutation (1,000×).
