title: Copy number variation in bipolar disorder.
abstract: Large (>100 kb), rare (<1% in the population) copy number variants (CNVs) have been shown to confer risk for schizophrenia (SZ), but the findings for bipolar disorder (BD) are less clear. In a new BD sample from the United Kingdom (n=2591), we have examined the occurrence of CNVs and compared this with previously reported samples of 6882 SZ and 8842 control subjects. When combined with previous data, we find evidence for a contribution to BD for three SZ-associated CNV loci: duplications at 1q21.1 (P=0.022), deletions at 3q29 (P=0.03) and duplications at 16p11.2 (P=2.3 × 10(-4)). The latter survives multiple-testing correction for the number of recurrent large CNV loci in the genome. Genes in 20 regions (total of 55 genes) were enriched for rare exonic CNVs among BD cases, but none of these survives correction for multiple testing. Finally, our data provide strong support for the hypothesis of a lesser contribution of very large (>500 kb) CNVs in BD compared with SZ, most notably for deletions >1 Mb (P=9 × 10(-4)).
authors.affiliation: School of Biomedical and Healthcare Sciences, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK.
authors.forename: E K
authors.initials: EK
authors.lastname: Green
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: E
authors.initials: E
authors.lastname: Rees
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: J T R
authors.initials: JT
authors.lastname: Walters
authors.affiliation: Department of Psychiatry, School of Clinical and Experimental Medicine, National Centre for Mental Health, University of Birmingham, Birmingham, UK.
authors.forename: K-G
authors.initials: KG
authors.lastname: Smith
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: L
authors.initials: L
authors.lastname: Forty
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: D
authors.initials: D
authors.lastname: Grozeva
authors.affiliation: Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Moran
authors.affiliation: Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Sklar
authors.affiliation: Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.|Division of Psychiatric Genomics in the Department of Psychiatry, Friedman Brain Institute, and Institute for Genomics and Multiscale Biology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ripke
authors.affiliation: Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Chambert
authors.affiliation: Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Genovese
authors.affiliation: Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: McCarroll
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: I
authors.initials: I
authors.lastname: Jones
authors.affiliation: Department of Psychiatry, School of Clinical and Experimental Medicine, National Centre for Mental Health, University of Birmingham, Birmingham, UK.
authors.forename: L
authors.initials: L
authors.lastname: Jones
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Owen
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: M C
authors.initials: MC
authors.lastname: O'Donovan
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: N
authors.initials: N
authors.lastname: Craddock
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: G
authors.initials: G
authors.lastname: Kirov
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000235:genetics; D044465:White People