Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation.. Homo sapiens

The Affymetrix CytoScan HD 2.5M and Illumina HumanOmni2.5 arrays are high resolution SNP platform for studying copy number variations in the human genome. Both platforms have widely being used in both clinical and research settings for identifying causative variants as well as interrogating the genome for benign variants. We employed both platforms to investigate the risk factor CNVs in trios diagnosed with OCD. We genotyped 307 unrelated probands (including 174 complete parent-child trios; mean age of probands 7.9±3.5 years) and compared their genotypes to those of 3,861 population controls, in order to identify rare CNVs (<0.5% frequency) of at least 15 kb in size that might contribute to OCD. We uncovered de novo CNVs and Decipher Syndromes in probands. We have identified additional potentially risk factor CNVs impacting the coding sequencing of genes involved in brain functions. Overall design: We employed Affymetrix Chromsome Analysis Suite (ChAS), iPattern, Nexus, and Partek algorithms to call CNVs from the CytoScan HD array data. Similarly, we detected CNVs from OMNI2.5M microarray data using iPattern, PennCNV, CNVPartition, and QuantiSNP. We defined a stringent set of variants when each variant was called by at least by two algorithms. We defined the ancestry and relatedness of the samples using PLINK