Although complex disorders such as schizophrenia have a heritable component, identifying the genetic components associated has been very difficult. Walsh et al. found that multiple, individually rare, structural mutations (genomic microdeletions and -duplications) occurred more frequently in 150 individuals with schizophrenia than in controls. The enrichment was more than threefold among schizophrenia cases generally and more than fourfold among schizophrenia cases with onset by age 18. The genes disrupted by the genomic breakpoints of mutations in the schizophrenia patients were not random but were disproportionately members of pathways controlling neuronal signaling and brain development.
T. Walsh, J. M. McClellan, S. E. McCarthy, A. M. Addington, S. B. Pierce, G. M. Cooper, A. S. Nord, M. Kusenda, D. Malhotra, A. Bhandari, S. M. Stray, C. F. Rippey, P. Roccanova, V. Makarov, B. Lakshmi, R. L. Findling, L. Sikich, T. Stromberg, B. Merriman, N. Gogtay, P. Butler, K. Eckstrand, L. Noory, P. Gochman, R. Long, Z. Chen, S. Davis, C. Baker, E. E. Eichler, P. S. Meltzer, S. F. Nelson, A. B. Singleton, M. K. Lee, J. L. Rapoport, M.-C. King, J. Sebat, Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320, 539-543 (2008). [Abstract] [Full Text]