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.
N1 - Funding Information:
This research was supported by grants from the MRC, the Wellcome Trust and by NIMH (USA) CONTE: 2 P50 MH066392-05A1. This study makes use of data generated by the Wellcome Trust Case Control Consortium (full list of contributors is presented in the Supplementary Material). Funding for that project was provided by the Wellcome Trust under award 076113.
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.
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U2 - 10.1093/hmg/ddp043
DO - 10.1093/hmg/ddp043
M3 - Article
C2 - 19181681
AN - SCOPUS:64549147485
SN - 0964-6906
VL - 18
SP - 1497
EP - 1503
JO - Human molecular genetics
JF - Human molecular genetics
IS - 8
ER -