Phenotypic Association Analyses With Copy Number Variation in Recurrent Depressive Disorder

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • James J. H. Rucker, South London & Maudsley Natl Hlth Serv Fdn Trust, South London & Maudsley NHS Trust, Natl Inst Hlth Res, Biomed Res Ctr
  • ,
  • Katherine E. Tansey, Cardiff Univ, Cardiff University, Neurosci & Mental Hlth Res Inst, MRC, Ctr Neuropsychiat Genet & Genom
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  • Margarita Rivera, Univ Granada, University of Granada, CIBERSaM, Biomed Res Ctr, Sect Psychiat,Inst Neurosci
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  • Dalila Pinto, Mt Sinai Sch Med, Mount Sinai School of Medicine, Mindich Child Hlth & Dev Inst, Seaver Autism Ctr, Dept Genom Sci
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  • Sarah Cohen-Woods, Kings Coll London, Kings College London, University of London, Inst Psychiat, MRC, Social Genet & Dev Psychiat Ctr
  • ,
  • Rudolf Uher, Dalhousie Univ, Dalhousie University, Dept Psychiat
  • ,
  • Katherine J. Aitchison, Univ Alberta, University of Alberta, Dept Psychiat
  • ,
  • Nick Craddock, Cardiff Univ, Cardiff University, Neurosci & Mental Hlth Res Inst, MRC, Ctr Neuropsychiat Genet & Genom
  • ,
  • Michael J. Owen, Cardiff Univ, Cardiff University, Neurosci & Mental Hlth Res Inst, MRC, Ctr Neuropsychiat Genet & Genom
  • ,
  • Lisa Jones, Univ Birmingham, University of Birmingham, Dept Psychiat
  • ,
  • Ian Jones, Cardiff Univ, Cardiff University, Neurosci & Mental Hlth Res Inst, MRC, Ctr Neuropsychiat Genet & Genom
  • ,
  • Ania Korszun, Queen Mary Univ London, Queen Mary University London, University of London, Barts & London Sch Med & Denistry
  • ,
  • Michael R. Barnes, GlaxoSmithKline, GlaxoSmithKline
  • ,
  • Martin Preisig, Univ Lausanne Hosp, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Dept Psychiat
  • ,
  • Ole Mors
  • Wolfgang Maier, Univ Bonn, University of Bonn, Dept Psychiat
  • ,
  • John Rice, Washington Univ, Washington University (WUSTL), Sch Med, Dept Psychiat
  • ,
  • Marcella Rietschel
  • ,
  • Florian Holsboer, Max Planck Inst Psychiat, Max Planck Society
  • ,
  • Anne E. Farmer, South London & Maudsley Natl Hlth Serv Fdn Trust, South London & Maudsley NHS Trust, Natl Inst Hlth Res, Biomed Res Ctr
  • ,
  • Ian W. Craig, Kings Coll London, Kings College London, University of London, Inst Psychiat, MRC, Social Genet & Dev Psychiat Ctr
  • ,
  • Stephen W. Scherer, Univ Toronto, University of Toronto, Dept Mol Genet
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  • Peter McGuffin, South London & Maudsley Natl Hlth Serv Fdn Trust, South London & Maudsley NHS Trust, Natl Inst Hlth Res, Biomed Res Ctr
  • ,
  • Gerome Breen, South London & Maudsley Natl Hlth Serv Fdn Trust, South London & Maudsley NHS Trust, Natl Inst Hlth Res, Biomed Res Ctr
  • Centre for Psychiatric Research

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.

Original languageEnglish
JournalBiological Psychiatry
Volume79
Issue4
Pages (from-to)329-336
Number of pages8
ISSN0006-3223
DOIs
Publication statusPublished - 15 Feb 2016

    Research areas

  • Affective disorders, Copy number variation, Depression, Genetics, Phenotypes, SEX-CHROMOSOME ABNORMALITIES, HIDDEN-MARKOV MODEL, SNP GENOTYPING DATA, UNIPARENTAL DISOMY, BIPOLAR DISORDER, MAJOR DEPRESSION, SCHIZOPHRENIA, VARIANTS, MOSAICISM, DUPLICATIONS

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