Premium
Reduced burden of very large and rare CNV s in bipolar affective disorder
Author(s) -
Grozeva Detelina,
Kirov George,
Conrad Donald F,
Barnes Chris P,
Hurles Matthew,
Owen Michael J,
O'Donovan Michael C,
Craddock Nick
Publication year - 2013
Publication title -
bipolar disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.285
H-Index - 129
eISSN - 1399-5618
pISSN - 1398-5647
DOI - 10.1111/bdi.12125
Subject(s) - bipolar disorder , psychology , psychiatry , clinical psychology , medicine , mood
Objectives Large, rare chromosomal copy number variants ( CNV s) have been shown to increase the risk for schizophrenia and other neuropsychiatric disorders including autism, attention‐deficit hyperactivity disorder, learning difficulties, and epilepsy. Their role in bipolar disorder ( BD ) is less clear. There are no reports of an increase in large, rare CNV s in BD in general, but some have reported an increase in early‐onset cases. We previously found that the rate of such CNV s in individuals with BD was not increased, even in early‐onset cases. Our aim here was to examine the rate of large rare CNV s in BD in comparison with a new large independent reference sample from the same country. Methods We studied the CNV s in a case–control sample consisting of 1,650 BD cases (reported previously) and 10,259 reference individuals without a known psychiatric disorder who took part in the original Wellcome Trust Case Control Consortium ( WTCCC ) study. The 10,259 reference individuals were affected with six non‐psychiatric disorders (coronary artery disease, types 1 and 2 diabetes, hypertension, Crohn's disease, and rheumatoid arthritis). Affymetrix 500K array genotyping data were used to call the CNV s. Results The rate of CNV s > 100 kb was not statistically different between cases and controls. The rate of very large (defined as > 1 Mb) and rare (< 1%) CNV s was significantly lower in patients with BD compared with the reference group. CNV loci associated with schizophrenia were not enriched in BD and, in fact, cases of BD had the lowest number of such CNV s compared with any of the WTCCC cohorts; this finding held even for the early‐onset BD cases. Conclusions Schizophrenia and BD differ with respect to CNV burden and association with specific CNV s. Our findings support the hypothesis that BD is etiologically distinct from schizophrenia with respect to large, rare CNV s and the accompanying associated neurodevelopmental abnormalities.