Another concern on wave adjustment is that it may create false positive CNVs, by making signals in some genomic regions deviate from zero. Since false positive calls are more difficult to assess than false negatives, to investigate this issue, we took advantage of the three large sibships (each with 7–12 siblings) in this pedigree (Supplementary Figure 7). We define ‘unique’ CNV calls in the sibships as those detected in only one individual (but not in the parents or other family members). A ‘unique’ CNV can occur if (i) the CNV is a false positive call; (ii) both parents have normal copies, and the offspring has copy number change due to de novo event; or (iii) at least one parent has copy number change but due to false negative calls, the copy number change is not detected in the parents and are also not detected in any other siblings. In the context of this large pedigree, since the probability of (i) far exceeds both (ii) and (iii), it is reasonable to treat those ‘unique’ CNVs as false positive calls. Before signal
