Copy Number Variation and Schizophrenia (autism)

Schizophrenia Bulletin Advance Access originally published online on November 5, 2008
Schizophrenia Bulletin 2009 35(1):9-12; doi:10.1093/schbul/sbn147




© The Author 2008. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.


Copy Number Variation and Schizophrenia
David St Clair1,2
2 Institute of Medical Sciences, University of Aberdeen

1 To whom correspondence should be addressed; David St Clair, Professor of Psychiatry, University of Aberdeen, Institute of Medical Science, Foresterhill, Aberdeen, AB25 2ZD, email: mmbl@bigpond.com

Over the last 12 months, a series of major articles have reported associations with schizophrenia of copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 22q12, and Neurexin 1 loci. These are rare high-penetrant mutations that increase risk not only of schizophrenia but also of a range of other psychiatric disorders including autism and mental retardation. In some cases, the same phenotype can occur irrespective of whether the copy number variant causes a deletion or duplication. Some of these mutations occur at very high rates in human populations, but because of reduced fecundity associated with major psychiatric disorders the overall frequency in the population remains low. These new findings raise fundamental clinical and scientific questions concerning classification of major neuropsychiatric disorders, modes of inheritance, diagnostics, and genetic counseling. Although the loci identified so far account for only a small proportion of cases, many more are likely to be discovered over the next few years. A major focus of research will be to identify the key, the genetic and environmental determinants of schizophrenia risk in carriers of these copy number variants, and to discover whether their rates of mutation are unstable or fixed.


Keywords: schizophrenia / genome / CNV