Support for the involvement of large copy number variants in the pathogenesis of schizophrenia

George Kirov, Detelina Grozeva, Nadine Norton, Dobril Ivanov, Kiran K. Mantripragada, Peter Holmans, Nick Craddock, Michael J. Owen, Michael C. O'Donovan

Research output: Contribution to journalArticle

309 Citations (Scopus)

Abstract

We investigated the involvement of rare (<1%) c0opy number variants (CNVs) in 471 cases of schizophrenia and 2792 controls that had been genotyped using the Affymetrix GeneChip® 500K Mapping Array. Large CNVs >1 Mb were 2.26 times more common in cases (P = 0.00027), with the effect coming mostly from deletions (odds ratio, OR = 4.53, P = 0.00013) although duplications were also more common (OR = 1.71, P = 0.04). Two large deletions were found in two cases each, but in no controls: a deletion at 22q11.2 known to be a susceptibility factor for schizophrenia and a deletion on 17p12, at 14.0-15.4 Mb. The latter is known to cause hereditary neuropathy with liability to pressure palsies. The same deletion was found in 6 of 4618 (0.13%) cases and 6 of 36 092 (0.017%) controls in the re-analysed data of two recent large CNV studies of schizophrenia (OR = 7.82, P = 0.001), with the combined significance level for all three studies achieving P = 5 × 10-5. One large duplication on 16p13.1, which has been previously implicated as a susceptibility factor for autism, was found in three cases and six controls (0.6% versus 0.2%, OR = 2.98, P = 0.13). We also provide the first support for a recently reported association between deletions at 15q11.2 and schizophrenia (P = 0.026). This study confirms the involvement of rare CNVs in the pathogenesis of schizophrenia and contributes to the growing list of specific CNVs that are implicated.

Original languageEnglish (US)
Pages (from-to)1497-1503
Number of pages7
JournalHuman Molecular Genetics
Volume18
Issue number8
DOIs
StatePublished - 2009
Externally publishedYes

Fingerprint

Schizophrenia
Autistic Disorder
Odds Ratio

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Kirov, G., Grozeva, D., Norton, N., Ivanov, D., Mantripragada, K. K., Holmans, P., ... O'Donovan, M. C. (2009). Support for the involvement of large copy number variants in the pathogenesis of schizophrenia. Human Molecular Genetics, 18(8), 1497-1503. https://doi.org/10.1093/hmg/ddp043

Support for the involvement of large copy number variants in the pathogenesis of schizophrenia. / Kirov, George; Grozeva, Detelina; Norton, Nadine; Ivanov, Dobril; Mantripragada, Kiran K.; Holmans, Peter; Craddock, Nick; Owen, Michael J.; O'Donovan, Michael C.

In: Human Molecular Genetics, Vol. 18, No. 8, 2009, p. 1497-1503.

Research output: Contribution to journalArticle

Kirov, G, Grozeva, D, Norton, N, Ivanov, D, Mantripragada, KK, Holmans, P, Craddock, N, Owen, MJ & O'Donovan, MC 2009, 'Support for the involvement of large copy number variants in the pathogenesis of schizophrenia', Human Molecular Genetics, vol. 18, no. 8, pp. 1497-1503. https://doi.org/10.1093/hmg/ddp043
Kirov, George ; Grozeva, Detelina ; Norton, Nadine ; Ivanov, Dobril ; Mantripragada, Kiran K. ; Holmans, Peter ; Craddock, Nick ; Owen, Michael J. ; O'Donovan, Michael C. / Support for the involvement of large copy number variants in the pathogenesis of schizophrenia. In: Human Molecular Genetics. 2009 ; Vol. 18, No. 8. pp. 1497-1503.
@article{086e5b7e87f440f1853749761f76fa48,
title = "Support for the involvement of large copy number variants in the pathogenesis of schizophrenia",
abstract = "We investigated the involvement of rare (<1{\%}) c0opy number variants (CNVs) in 471 cases of schizophrenia and 2792 controls that had been genotyped using the Affymetrix GeneChip{\circledR} 500K Mapping Array. Large CNVs >1 Mb were 2.26 times more common in cases (P = 0.00027), with the effect coming mostly from deletions (odds ratio, OR = 4.53, P = 0.00013) although duplications were also more common (OR = 1.71, P = 0.04). Two large deletions were found in two cases each, but in no controls: a deletion at 22q11.2 known to be a susceptibility factor for schizophrenia and a deletion on 17p12, at 14.0-15.4 Mb. The latter is known to cause hereditary neuropathy with liability to pressure palsies. The same deletion was found in 6 of 4618 (0.13{\%}) cases and 6 of 36 092 (0.017{\%}) controls in the re-analysed data of two recent large CNV studies of schizophrenia (OR = 7.82, P = 0.001), with the combined significance level for all three studies achieving P = 5 × 10-5. One large duplication on 16p13.1, which has been previously implicated as a susceptibility factor for autism, was found in three cases and six controls (0.6{\%} versus 0.2{\%}, OR = 2.98, P = 0.13). We also provide the first support for a recently reported association between deletions at 15q11.2 and schizophrenia (P = 0.026). This study confirms the involvement of rare CNVs in the pathogenesis of schizophrenia and contributes to the growing list of specific CNVs that are implicated.",
author = "George Kirov and Detelina Grozeva and Nadine Norton and Dobril Ivanov and Mantripragada, {Kiran K.} and Peter Holmans and Nick Craddock and Owen, {Michael J.} and O'Donovan, {Michael C.}",
year = "2009",
doi = "10.1093/hmg/ddp043",
language = "English (US)",
volume = "18",
pages = "1497--1503",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "8",

}

TY - JOUR

T1 - Support for the involvement of large copy number variants in the pathogenesis of schizophrenia

AU - Kirov, George

AU - Grozeva, Detelina

AU - Norton, Nadine

AU - Ivanov, Dobril

AU - Mantripragada, Kiran K.

AU - Holmans, Peter

AU - Craddock, Nick

AU - Owen, Michael J.

AU - O'Donovan, Michael C.

PY - 2009

Y1 - 2009

N2 - We investigated the involvement of rare (<1%) c0opy number variants (CNVs) in 471 cases of schizophrenia and 2792 controls that had been genotyped using the Affymetrix GeneChip® 500K Mapping Array. Large CNVs >1 Mb were 2.26 times more common in cases (P = 0.00027), with the effect coming mostly from deletions (odds ratio, OR = 4.53, P = 0.00013) although duplications were also more common (OR = 1.71, P = 0.04). Two large deletions were found in two cases each, but in no controls: a deletion at 22q11.2 known to be a susceptibility factor for schizophrenia and a deletion on 17p12, at 14.0-15.4 Mb. The latter is known to cause hereditary neuropathy with liability to pressure palsies. The same deletion was found in 6 of 4618 (0.13%) cases and 6 of 36 092 (0.017%) controls in the re-analysed data of two recent large CNV studies of schizophrenia (OR = 7.82, P = 0.001), with the combined significance level for all three studies achieving P = 5 × 10-5. One large duplication on 16p13.1, which has been previously implicated as a susceptibility factor for autism, was found in three cases and six controls (0.6% versus 0.2%, OR = 2.98, P = 0.13). We also provide the first support for a recently reported association between deletions at 15q11.2 and schizophrenia (P = 0.026). This study confirms the involvement of rare CNVs in the pathogenesis of schizophrenia and contributes to the growing list of specific CNVs that are implicated.

AB - We investigated the involvement of rare (<1%) c0opy number variants (CNVs) in 471 cases of schizophrenia and 2792 controls that had been genotyped using the Affymetrix GeneChip® 500K Mapping Array. Large CNVs >1 Mb were 2.26 times more common in cases (P = 0.00027), with the effect coming mostly from deletions (odds ratio, OR = 4.53, P = 0.00013) although duplications were also more common (OR = 1.71, P = 0.04). Two large deletions were found in two cases each, but in no controls: a deletion at 22q11.2 known to be a susceptibility factor for schizophrenia and a deletion on 17p12, at 14.0-15.4 Mb. The latter is known to cause hereditary neuropathy with liability to pressure palsies. The same deletion was found in 6 of 4618 (0.13%) cases and 6 of 36 092 (0.017%) controls in the re-analysed data of two recent large CNV studies of schizophrenia (OR = 7.82, P = 0.001), with the combined significance level for all three studies achieving P = 5 × 10-5. One large duplication on 16p13.1, which has been previously implicated as a susceptibility factor for autism, was found in three cases and six controls (0.6% versus 0.2%, OR = 2.98, P = 0.13). We also provide the first support for a recently reported association between deletions at 15q11.2 and schizophrenia (P = 0.026). This study confirms the involvement of rare CNVs in the pathogenesis of schizophrenia and contributes to the growing list of specific CNVs that are implicated.

UR - http://www.scopus.com/inward/record.url?scp=64549147485&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=64549147485&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddp043

DO - 10.1093/hmg/ddp043

M3 - Article

C2 - 19181681

AN - SCOPUS:64549147485

VL - 18

SP - 1497

EP - 1503

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 8

ER -