Rare copy number variants: a point of rarity in genetic risk for bipolar disorder and schizophrenia

Detelina Grozeva, George Kirov, Dobril Ivanov, Ian R Jones, Lisa Jones, Elaine K Green, David Malcolm St Clair, Allan H Young, Nicol Ferrier, Anne E Farmer, Peter McGuffin, Peter A Holmans, Michael J Owen, Michael C O'Donovan, Nick Craddock, Wellcome Trust Case Control Consortium

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Context Recent studies suggest that copy number variation in the human genome is extensive and may play an important role in susceptibility to disease, including neuropsychiatric disorders such as schizophrenia and autism. The possible involvement of copy number variants (CNVs) in bipolar disorder has received little attention to date.

Objectives To determine whether large (>100 000 base pairs) and rare (found in <1% of the population) CNVs are associated with susceptibility to bipolar disorder and to compare with findings in schizophrenia.

Design A genome-wide survey of large, rare CNVs in a case-control sample using a high-density microarray.

Setting The Wellcome Trust Case Control Consortium.

Participants There were 1697 cases of bipolar disorder and 2806 nonpsychiatric controls. All participants were white UK residents.

Main Outcome Measures Overall load of CNVs and presence of rare CNVs.

Results The burden of CNVs in bipolar disorder was not increased compared with controls and was significantly less than in schizophrenia cases. The CNVs previously implicated in the etiology of schizophrenia were not more common in cases with bipolar disorder.

Conclusions Schizophrenia and bipolar disorder differ with respect to CNV burden in general and association with specific CNVs in particular. Our data are consistent with the possibility that possession of large, rare deletions may modify the phenotype in those at risk of psychosis: those possessing such events are more likely to be diagnosed as having schizophrenia, and those without them are more likely to be diagnosed as having bipolar disorder.
Original languageEnglish
Pages (from-to)318-327
Number of pages10
JournalArchives of General Psychiatry
Volume67
Issue number4
DOIs
Publication statusPublished - Apr 2010

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Bipolar Disorder
Schizophrenia
Disease Susceptibility
Human Genome
Autistic Disorder
Genetic Risk
Base Pairing
Psychotic Disorders
Outcome Assessment (Health Care)
Genome
Phenotype
Population

Cite this

Grozeva, D., Kirov, G., Ivanov, D., Jones, I. R., Jones, L., Green, E. K., ... Wellcome Trust Case Control Consortium (2010). Rare copy number variants: a point of rarity in genetic risk for bipolar disorder and schizophrenia. Archives of General Psychiatry, 67(4), 318-327. https://doi.org/10.1001/archgenpsychiatry.2010.25

Rare copy number variants : a point of rarity in genetic risk for bipolar disorder and schizophrenia. / Grozeva, Detelina; Kirov, George; Ivanov, Dobril; Jones, Ian R; Jones, Lisa; Green, Elaine K; St Clair, David Malcolm; Young, Allan H; Ferrier, Nicol; Farmer, Anne E; McGuffin, Peter; Holmans, Peter A; Owen, Michael J; O'Donovan, Michael C; Craddock, Nick; Wellcome Trust Case Control Consortium.

In: Archives of General Psychiatry, Vol. 67, No. 4, 04.2010, p. 318-327.

Research output: Contribution to journalArticle

Grozeva, D, Kirov, G, Ivanov, D, Jones, IR, Jones, L, Green, EK, St Clair, DM, Young, AH, Ferrier, N, Farmer, AE, McGuffin, P, Holmans, PA, Owen, MJ, O'Donovan, MC, Craddock, N & Wellcome Trust Case Control Consortium 2010, 'Rare copy number variants: a point of rarity in genetic risk for bipolar disorder and schizophrenia', Archives of General Psychiatry, vol. 67, no. 4, pp. 318-327. https://doi.org/10.1001/archgenpsychiatry.2010.25
Grozeva, Detelina ; Kirov, George ; Ivanov, Dobril ; Jones, Ian R ; Jones, Lisa ; Green, Elaine K ; St Clair, David Malcolm ; Young, Allan H ; Ferrier, Nicol ; Farmer, Anne E ; McGuffin, Peter ; Holmans, Peter A ; Owen, Michael J ; O'Donovan, Michael C ; Craddock, Nick ; Wellcome Trust Case Control Consortium. / Rare copy number variants : a point of rarity in genetic risk for bipolar disorder and schizophrenia. In: Archives of General Psychiatry. 2010 ; Vol. 67, No. 4. pp. 318-327.
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abstract = "Context Recent studies suggest that copy number variation in the human genome is extensive and may play an important role in susceptibility to disease, including neuropsychiatric disorders such as schizophrenia and autism. The possible involvement of copy number variants (CNVs) in bipolar disorder has received little attention to date.Objectives To determine whether large (>100 000 base pairs) and rare (found in <1{\%} of the population) CNVs are associated with susceptibility to bipolar disorder and to compare with findings in schizophrenia.Design A genome-wide survey of large, rare CNVs in a case-control sample using a high-density microarray.Setting The Wellcome Trust Case Control Consortium.Participants There were 1697 cases of bipolar disorder and 2806 nonpsychiatric controls. All participants were white UK residents.Main Outcome Measures Overall load of CNVs and presence of rare CNVs.Results The burden of CNVs in bipolar disorder was not increased compared with controls and was significantly less than in schizophrenia cases. The CNVs previously implicated in the etiology of schizophrenia were not more common in cases with bipolar disorder.Conclusions Schizophrenia and bipolar disorder differ with respect to CNV burden in general and association with specific CNVs in particular. Our data are consistent with the possibility that possession of large, rare deletions may modify the phenotype in those at risk of psychosis: those possessing such events are more likely to be diagnosed as having schizophrenia, and those without them are more likely to be diagnosed as having bipolar disorder.",
author = "Detelina Grozeva and George Kirov and Dobril Ivanov and Jones, {Ian R} and Lisa Jones and Green, {Elaine K} and {St Clair}, {David Malcolm} and Young, {Allan H} and Nicol Ferrier and Farmer, {Anne E} and Peter McGuffin and Holmans, {Peter A} and Owen, {Michael J} and O'Donovan, {Michael C} and Nick Craddock and {Wellcome Trust Case Control Consortium}",
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AU - Grozeva, Detelina

AU - Kirov, George

AU - Ivanov, Dobril

AU - Jones, Ian R

AU - Jones, Lisa

AU - Green, Elaine K

AU - St Clair, David Malcolm

AU - Young, Allan H

AU - Ferrier, Nicol

AU - Farmer, Anne E

AU - McGuffin, Peter

AU - Holmans, Peter A

AU - Owen, Michael J

AU - O'Donovan, Michael C

AU - Craddock, Nick

AU - Wellcome Trust Case Control Consortium

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N2 - Context Recent studies suggest that copy number variation in the human genome is extensive and may play an important role in susceptibility to disease, including neuropsychiatric disorders such as schizophrenia and autism. The possible involvement of copy number variants (CNVs) in bipolar disorder has received little attention to date.Objectives To determine whether large (>100 000 base pairs) and rare (found in <1% of the population) CNVs are associated with susceptibility to bipolar disorder and to compare with findings in schizophrenia.Design A genome-wide survey of large, rare CNVs in a case-control sample using a high-density microarray.Setting The Wellcome Trust Case Control Consortium.Participants There were 1697 cases of bipolar disorder and 2806 nonpsychiatric controls. All participants were white UK residents.Main Outcome Measures Overall load of CNVs and presence of rare CNVs.Results The burden of CNVs in bipolar disorder was not increased compared with controls and was significantly less than in schizophrenia cases. The CNVs previously implicated in the etiology of schizophrenia were not more common in cases with bipolar disorder.Conclusions Schizophrenia and bipolar disorder differ with respect to CNV burden in general and association with specific CNVs in particular. Our data are consistent with the possibility that possession of large, rare deletions may modify the phenotype in those at risk of psychosis: those possessing such events are more likely to be diagnosed as having schizophrenia, and those without them are more likely to be diagnosed as having bipolar disorder.

AB - Context Recent studies suggest that copy number variation in the human genome is extensive and may play an important role in susceptibility to disease, including neuropsychiatric disorders such as schizophrenia and autism. The possible involvement of copy number variants (CNVs) in bipolar disorder has received little attention to date.Objectives To determine whether large (>100 000 base pairs) and rare (found in <1% of the population) CNVs are associated with susceptibility to bipolar disorder and to compare with findings in schizophrenia.Design A genome-wide survey of large, rare CNVs in a case-control sample using a high-density microarray.Setting The Wellcome Trust Case Control Consortium.Participants There were 1697 cases of bipolar disorder and 2806 nonpsychiatric controls. All participants were white UK residents.Main Outcome Measures Overall load of CNVs and presence of rare CNVs.Results The burden of CNVs in bipolar disorder was not increased compared with controls and was significantly less than in schizophrenia cases. The CNVs previously implicated in the etiology of schizophrenia were not more common in cases with bipolar disorder.Conclusions Schizophrenia and bipolar disorder differ with respect to CNV burden in general and association with specific CNVs in particular. Our data are consistent with the possibility that possession of large, rare deletions may modify the phenotype in those at risk of psychosis: those possessing such events are more likely to be diagnosed as having schizophrenia, and those without them are more likely to be diagnosed as having bipolar disorder.

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