Impact of IQ on the diagnostic yield of chromosomal microarray in a community sample of adults with schizophrenia

The Affymetrix Genome-Wide Human SNP 6.0 and CytoScan HD arrays are high-resolution SNP platforms for studying copy number variations in the human genome. It is widely being used in both clinical and research settings for identifying causative variants as well as interrogating the genome for benign variants. We employed this platform to investigate the burden of clinically relevant rare (<0.1% in population controls) CNVs in individuals with schizophrenia, stratified by IQ group. We genotyped 540 unrelated probands with schizophrenia and applied rigorous methods to detect genome-wide CNVs. All rare CNV >500 kb and all rare exonic CNV >100 kb were adjudicated for clinical relevance following the American College of Medical Genetics guidelines for CNV interpretation. Our results revealed that burden of pathogenic CNVs is significantly greater for individuals with schizophrenia and low IQ compared to those with normal to superior IQ All samples met the Affymetrix quality control cut-offs. We only included CNVs that were >10 kb, identified by at least two CNV calling algorithms (two of ChAS, iPattern, or Genotyping Console for the CytoScan HD array and two of iPattern, Birdsuite or Genotyping Console for the Affymetrix 6.0 array), spanning 10 consecutive array probes, and overlapping <75% of segmental duplications. We defined the ancestry and relatedness of the samples using PLINK.