High frequencies of de novo CNVs in bipolar disorder and schizophrenia.
Michaelson, Jacob J
Burdick, Katherine E
Gershon, Elliot S
Kelsoe, John R
Levy, Deborah L
Malhotra, Anil K
McMahon, Francis J
Nöthen, Markus M
Potash, James B
Schulze, Thomas G
AffiliationBeyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USA.
DNA Copy Number Variations
Genome-Wide Association Study
MetadataShow full item record
CitationHigh frequencies of de novo CNVs in bipolar disorder and schizophrenia. 2011, 72 (6):951-63 Neuron
AbstractWhile it is known that rare copy-number variants (CNVs) contribute to risk for some neuropsychiatric disorders, the role of CNVs in bipolar disorder is unclear. Here, we reasoned that a contribution of CNVs to mood disorders might be most evident for de novo mutations. We performed a genome-wide analysis of de novo CNVs in a cohort of 788 trios. Diagnoses of offspring included bipolar disorder (n = 185), schizophrenia (n = 177), and healthy controls (n = 426). Frequencies of de novo CNVs were significantly higher in bipolar disorder as compared with controls (OR = 4.8 [1.4,16.0], p = 0.009). De novo CNVs were particularly enriched among cases with an age at onset younger than 18 (OR = 6.3 [1.7,22.6], p = 0.006). We also confirmed a significant enrichment of de novo CNVs in schizophrenia (OR = 5.0 [1.5,16.8], p = 0.007). Our results suggest that rare spontaneous mutations are an important contributor to risk for bipolar disorder and other major neuropsychiatric diseases.
- De novo CNVs in bipolar disorder: recurrent themes or new directions?
- Authors: Girirajan S, Eichler EE
- Issue date: 2011 Dec 22
- De novo CNVs in bipolar affective disorder and schizophrenia.
- Authors: Georgieva L, Rees E, Moran JL, Chambert KD, Milanova V, Craddock N, Purcell S, Sklar P, McCarroll S, Holmans P, O'Donovan MC, Owen MJ, Kirov G
- Issue date: 2014 Dec 15
- Rare copy number variants: a point of rarity in genetic risk for bipolar disorder and schizophrenia.
- Authors: Grozeva D, Kirov G, Ivanov D, Jones IR, Jones L, Green EK, St Clair DM, Young AH, Ferrier N, Farmer AE, McGuffin P, Holmans PA, Owen MJ, O'Donovan MC, Craddock N, Wellcome Trust Case Control Consortium
- Issue date: 2010 Apr
- Reduced burden of very large and rare CNVs in bipolar affective disorder.
- Authors: Grozeva D, Kirov G, Conrad DF, Barnes CP, Hurles M, Owen MJ, O'Donovan MC, Craddock N
- Issue date: 2013 Dec
- De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia.
- Authors: Kirov G, Pocklington AJ, Holmans P, Ivanov D, Ikeda M, Ruderfer D, Moran J, Chambert K, Toncheva D, Georgieva L, Grozeva D, Fjodorova M, Wollerton R, Rees E, Nikolov I, van de Lagemaat LN, Bayés A, Fernandez E, Olason PI, Böttcher Y, Komiyama NH, Collins MO, Choudhary J, Stefansson K, Stefansson H, Grant SG, Purcell S, Sklar P, O'Donovan MC, Owen MJ
- Issue date: 2012 Feb