A genome-wide copy number variant (CNV) association study for schizophrenia (SZ), bipolar disorder (BP) and major depression (MD) will be conducted at deCODE genetics using a discovery sample of 2400 affected (800 SZ, 600 BP, 1,000 MD) and 20,000 controls. CNV data will be generated from the newly released HumanCNV370-Duo array designed by deCODE genetics and Illumina. In this array there are about 55,000 probes covering known and supsected CNV regions. Algorithms for data analysis are being developed at deCODE. Employees from the Research Institute of Biological Psychiatry (RIBP) of Copenhagen University Hospital and Center for Biological Sequence analysis (CBS) at Denmarks Technical University will work with deCODE on analyzing the data. CNVs associating with SZ, BP and MD in Iceland will be tested in SZ (n=800), BP (n=600) and MD (n=600) and control samples from RIBP using TaqMan probes to measure gene dosage. The confirmation and subsequent functional analysis, including gene expression, will be carried out at deCODE. Scientists from RIBP and CBS will test disease-specific candidate genes, derived from biological networks, for association to SZ, BP and MD in the Icelandic samples and confirm the findings in the RIBP samples. These methods, reduce the correction factor for false positive findings, as only a small subset of polymorphisms (SNPs and CNVs) will be investigated. This allows identification of susceptibility variants conferring low risk. Variants, associating with SZ, BP and MD in the follow-up samples, will be studied further by analyzing endophenotypes, i.e. treatment response, severity, etc. in the RIBPsamples. This will implement data stored in the Danish Psychiatric Biobank maintained at RIBP. Scientists from deCODE will work with scientists from RIBP on analyzing the endophenotypic data. Furthermore samples and phenotypic data from first degree relatives of SZ, BP and MD patients will be collected, analyzed and genotyped for CNVs and SNPs.