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Biol Psychiatry. 2016 Feb 15;79(4):329-36. doi: 10.1016/j.biopsych.2015.02.025. Epub 2015 Feb 25.

Phenotypic Association Analyses With Copy Number Variation in Recurrent Depressive Disorder.

Author information

1
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.
2
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.
3
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.
4
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.
5
Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, United Kingdom.
6
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.
7
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.
8
Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, Wales, United Kingdom.
9
Department of Psychiatry, University of Birmingham, Birmingham, United Kingdom.
10
Barts and The London School of Medicine and Denistry, Queen Mary University of London, London, United Kingdom.
11
GlaxoSmithKline, Verona, Italy, and Greenford.
12
Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
13
Centre of Psychiatric Research, Aarhus University Hospital, Risskov, Denmark.
14
Department of Psychiatry, University of Bonn, Bonn, Germany.
15
Department of Psychiatry, Washington University, St Louis, Missouri.
16
Central Institute of Mental Health, Mannheim.
17
Max Planck Institute of Psychiatry (FH), Munich, Germany.
18
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.
19
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.

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.

KEYWORDS:

Affective disorders; Copy number variation; Depression; Genetics; Phenotypes

PMID:
25861698
PMCID:
PMC4725574
DOI:
10.1016/j.biopsych.2015.02.025
[Indexed for MEDLINE]
Free PMC Article

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