Reduced burden of very large and rare CNVs in bipolar affective disorder

Detelina Grozeva, George Kirov, Don Conrad, Chris P. Barnes, Matthew Hurles, Michael J. Owen, Michael C. O'Donovan, Nick Craddock

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Objectives: Large, rare chromosomal copy number variants (CNVs) have been shown to increase the risk for schizophrenia and other neuropsychiatric disorders including autism, attention-deficit hyperactivity disorder, learning difficulties, and epilepsy. Their role in bipolar disorder (BD) is less clear. There are no reports of an increase in large, rare CNVs in BD in general, but some have reported an increase in early-onset cases. We previously found that the rate of such CNVs in individuals with BD was not increased, even in early-onset cases. Our aim here was to examine the rate of large rare CNVs in BD in comparison with a new large independent reference sample from the same country. Methods: We studied the CNVs in a case-control sample consisting of 1,650 BD cases (reported previously) and 10,259 reference individuals without a known psychiatric disorder who took part in the original Wellcome Trust Case Control Consortium (WTCCC) study. The 10,259 reference individuals were affected with six non-psychiatric disorders (coronary artery disease, types 1 and 2 diabetes, hypertension, Crohn's disease, and rheumatoid arthritis). Affymetrix 500K array genotyping data were used to call the CNVs. Results: The rate of CNVs > 100 kb was not statistically different between cases and controls. The rate of very large (defined as > 1 Mb) and rare (< 1%) CNVs was significantly lower in patients with BD compared with the reference group. CNV loci associated with schizophrenia were not enriched in BD and, in fact, cases of BD had the lowest number of such CNVs compared with any of the WTCCC cohorts; this finding held even for the early-onset BD cases. Conclusions: Schizophrenia and BD differ with respect to CNV burden and association with specific CNVs. Our findings support the hypothesis that BD is etiologically distinct from schizophrenia with respect to large, rare CNVs and the accompanying associated neurodevelopmental abnormalities.

Original languageEnglish (US)
Pages (from-to)893-898
Number of pages6
JournalBipolar Disorders
Volume15
Issue number8
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Fingerprint

Mood Disorders
Bipolar Disorder
Schizophrenia
Attention Deficit Disorder with Hyperactivity
Autistic Disorder
Type 1 Diabetes Mellitus
Crohn Disease
Type 2 Diabetes Mellitus
Psychiatry
Case-Control Studies
Coronary Artery Disease
Epilepsy
Rheumatoid Arthritis
Learning
Hypertension

Keywords

  • Bipolar disorder
  • CNV
  • Schizophrenia
  • WTCCC

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Grozeva, D., Kirov, G., Conrad, D., Barnes, C. P., Hurles, M., Owen, M. J., ... Craddock, N. (2013). Reduced burden of very large and rare CNVs in bipolar affective disorder. Bipolar Disorders, 15(8), 893-898. https://doi.org/10.1111/bdi.12125

Reduced burden of very large and rare CNVs in bipolar affective disorder. / Grozeva, Detelina; Kirov, George; Conrad, Don; Barnes, Chris P.; Hurles, Matthew; Owen, Michael J.; O'Donovan, Michael C.; Craddock, Nick.

In: Bipolar Disorders, Vol. 15, No. 8, 01.01.2013, p. 893-898.

Research output: Contribution to journalArticle

Grozeva, D, Kirov, G, Conrad, D, Barnes, CP, Hurles, M, Owen, MJ, O'Donovan, MC & Craddock, N 2013, 'Reduced burden of very large and rare CNVs in bipolar affective disorder', Bipolar Disorders, vol. 15, no. 8, pp. 893-898. https://doi.org/10.1111/bdi.12125
Grozeva, Detelina ; Kirov, George ; Conrad, Don ; Barnes, Chris P. ; Hurles, Matthew ; Owen, Michael J. ; O'Donovan, Michael C. ; Craddock, Nick. / Reduced burden of very large and rare CNVs in bipolar affective disorder. In: Bipolar Disorders. 2013 ; Vol. 15, No. 8. pp. 893-898.
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abstract = "Objectives: Large, rare chromosomal copy number variants (CNVs) have been shown to increase the risk for schizophrenia and other neuropsychiatric disorders including autism, attention-deficit hyperactivity disorder, learning difficulties, and epilepsy. Their role in bipolar disorder (BD) is less clear. There are no reports of an increase in large, rare CNVs in BD in general, but some have reported an increase in early-onset cases. We previously found that the rate of such CNVs in individuals with BD was not increased, even in early-onset cases. Our aim here was to examine the rate of large rare CNVs in BD in comparison with a new large independent reference sample from the same country. Methods: We studied the CNVs in a case-control sample consisting of 1,650 BD cases (reported previously) and 10,259 reference individuals without a known psychiatric disorder who took part in the original Wellcome Trust Case Control Consortium (WTCCC) study. The 10,259 reference individuals were affected with six non-psychiatric disorders (coronary artery disease, types 1 and 2 diabetes, hypertension, Crohn's disease, and rheumatoid arthritis). Affymetrix 500K array genotyping data were used to call the CNVs. Results: The rate of CNVs > 100 kb was not statistically different between cases and controls. The rate of very large (defined as > 1 Mb) and rare (< 1{\%}) CNVs was significantly lower in patients with BD compared with the reference group. CNV loci associated with schizophrenia were not enriched in BD and, in fact, cases of BD had the lowest number of such CNVs compared with any of the WTCCC cohorts; this finding held even for the early-onset BD cases. Conclusions: Schizophrenia and BD differ with respect to CNV burden and association with specific CNVs. Our findings support the hypothesis that BD is etiologically distinct from schizophrenia with respect to large, rare CNVs and the accompanying associated neurodevelopmental abnormalities.",
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