title: Phenotypic Association Analyses With Copy Number Variation in Recurrent Depressive Disorder.
abstract: BACKGROUND
  Defining the molecular genomic basis of the likelihood of developing depressive disorder is a considerable challenge. We previously associated rare, exonic deletion copy number variants (CNV) with recurrent depressive disorder (RDD). Sex chromosome abnormalities also have been observed to co-occur with RDD.
  
  
  METHODS
  In this reanalysis of our RDD dataset (N = 3106 cases; 459 screened control samples and 2699 population control samples), we further investigated the role of larger CNVs and chromosomal abnormalities in RDD and performed association analyses with clinical data derived from this dataset.
  
  
  RESULTS
  We found an enrichment of Turner's syndrome among cases of depression compared with the frequency observed in a large population sample (N = 34,910) of live-born infants collected in Denmark (two-sided p = .023, odds ratio = 7.76 [95% confidence interval = 1.79-33.6]), a case of diploid/triploid mosaicism, and several cases of uniparental isodisomy. In contrast to our previous analysis, large deletion CNVs were no more frequent in cases than control samples, although deletion CNVs in cases contained more genes than control samples (two-sided p = .0002).
  
  
  CONCLUSIONS
  After statistical correction for multiple comparisons, our data do not support a substantial role for CNVs in RDD, although (as has been observed in similar samples) occasional cases may harbor large variants with etiological significance. Genetic pleiotropy and sample heterogeneity suggest that very large sample sizes are required to study conclusively the role of genetic variation in mood disorders.
authors: Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, United Kingdom; National Institute for Health Research Biomedical Research Centre, South London and Maudsley National Health Service Foundation Trust and Institute of Psychiatry, King's College London. Electronic address: james.rucker@kcl.ac.uk.
authors: James J H
authors: JJ
authors: Rucker
authors: Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, United Kingdom; Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, Wales, United Kingdom.
authors: Katherine E
authors: KE
authors: Tansey
authors: Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, United Kingdom; Section of Psychiatry, Institute of Neurosciences, Biomedical Research Centre, CIBERSAM, University of Granada, Granada, Spain.
authors: Margarita
authors: M
authors: Rivera
authors: The Centre for Applied Genomics and Program in Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada; Departments of Psychiatry and Genetics and Genomic Sciences, Seaver Autism Center, The Mindich Child Health & Development Institute, Mount Sinai School of Medicine, New York, New York.
authors: Dalila
authors: D
authors: Pinto
authors: Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, United Kingdom.
authors: Sarah
authors: S
authors: Cohen-Woods
authors: Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, United Kingdom; Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
authors: Rudolf
authors: R
authors: Uher
authors: Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, United Kingdom; Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada.
authors: Katherine J
authors: KJ
authors: Aitchison
authors: Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, Wales, United Kingdom.
authors: Nick
authors: N
authors: Craddock
authors: Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, Wales, United Kingdom.
authors: Michael J
authors: MJ
authors: Owen
authors: Department of Psychiatry, University of Birmingham, Birmingham, United Kingdom.
authors: Lisa
authors: L
authors: Jones
authors: Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, Wales, United Kingdom.
authors: Ian
authors: I
authors: Jones
authors: Barts and The London School of Medicine and Denistry, Queen Mary University of London, London, United Kingdom.
authors: Ania
authors: A
authors: Korszun
authors: GlaxoSmithKline, Verona, Italy, and Greenford.
authors: Michael R
authors: MR
authors: Barnes
authors: Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
authors: Martin
authors: M
authors: Preisig
authors: Centre of Psychiatric Research, Aarhus University Hospital, Risskov, Denmark.
authors: Ole
authors: O
authors: Mors
authors: Department of Psychiatry, University of Bonn, Bonn, Germany.
authors: Wolfgang
authors: W
authors: Maier
authors: Department of Psychiatry, Washington University, St Louis, Missouri.
authors: John
authors: J
authors: Rice
authors: Central Institute of Mental Health, Mannheim.
authors: Marcella
authors: M
authors: Rietschel
authors: Max Planck Institute of Psychiatry (FH), Munich, Germany.
authors: Florian
authors: F
authors: Holsboer
authors: Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, United Kingdom; National Institute for Health Research Biomedical Research Centre, South London and Maudsley National Health Service Foundation Trust and Institute of Psychiatry, King's College London.
authors: Anne E
authors: AE
authors: Farmer
authors: Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, United Kingdom.
authors: Ian W
authors: IW
authors: Craig
authors: The Centre for Applied Genomics and Program in Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada; McLaughlin Centre and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors: Stephen W
authors: SW
authors: Scherer
authors: Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, United Kingdom; National Institute for Health Research Biomedical Research Centre, South London and Maudsley National Health Service Foundation Trust and Institute of Psychiatry, King's College London.
authors: Peter
authors: P
authors: McGuffin
authors: Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, United Kingdom; National Institute for Health Research Biomedical Research Centre, South London and Maudsley National Health Service Foundation Trust and Institute of Psychiatry, King's College London.
authors: Gerome
authors: G
authors: Breen
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002869:Chromosome Aberrations / Q000706:statistics & numerical data*; D056915:DNA Copy Number Variations / Q000235:genetics*; D030541:Databases, Genetic; D003866:Depressive Disorder / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D055815:Young Adult
keywords: Affective disorders; Copy number variation; Depression; Genetics; Phenotypes