Reciprocal duplication of the Williams-Beuren syndrome deletion on chromosome 7q11.23 is associated with schizophrenia

Mulle, Jennifer Gladys, Pulver, Ann E., McGrath, John A., Wolyniec, Paula S., Dodd, Anne F., Cutler, David J., Sebat, Jonathan, Malhotra, Dheeraj, Nestadt, Gerald, Conrad, Donald F., Hurles, Matthew, Barnes, Chris P., Ikeda, Masashi, Iwata, Nakao, Levinson, Douglas F., Gejman, Pablo V., Sanders, Alan R., Duan, Jubao, Mitchell, Adele A., Peter, Inga, Sklar, Pamela, O'Dushlaine, Colm T., Grozeva, Detelina, O'Donovan, Michael C., Owen, Michael J., Hultman, Christina M., Kahler, Anna K., Sullivan, Patrick F., The Molecular Genetics of Schizophrenia Consortium, Kirov, George, Warren, Stephen T. and Mowry, Bryan J. (2014) Reciprocal duplication of the Williams-Beuren syndrome deletion on chromosome 7q11.23 is associated with schizophrenia. Biological Psychiatry, 75 5: 371-377. doi:10.1016/j.biopsych.2013.05.040

Author Mulle, Jennifer Gladys
Pulver, Ann E.
McGrath, John A.
Wolyniec, Paula S.
Dodd, Anne F.
Cutler, David J.
Sebat, Jonathan
Malhotra, Dheeraj
Nestadt, Gerald
Conrad, Donald F.
Hurles, Matthew
Barnes, Chris P.
Ikeda, Masashi
Iwata, Nakao
Levinson, Douglas F.
Gejman, Pablo V.
Sanders, Alan R.
Duan, Jubao
Mitchell, Adele A.
Peter, Inga
Sklar, Pamela
O'Dushlaine, Colm T.
Grozeva, Detelina
O'Donovan, Michael C.
Owen, Michael J.
Hultman, Christina M.
Kahler, Anna K.
Sullivan, Patrick F.
The Molecular Genetics of Schizophrenia Consortium
Kirov, George
Warren, Stephen T.
Mowry, Bryan J.
Title Reciprocal duplication of the Williams-Beuren syndrome deletion on chromosome 7q11.23 is associated with schizophrenia
Journal name Biological Psychiatry   Check publisher's open access policy
ISSN 0006-3223
Publication date 2014-03-01
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.biopsych.2013.05.040
Open Access Status Not yet assessed
Volume 75
Issue 5
Start page 371
End page 377
Total pages 7
Place of publication Philadelphia PA, United States
Publisher Elsevier
Language eng
Formatted abstract

Several copy number variants (CNVs) have been implicated as susceptibility factors for schizophrenia (SZ). Some of these same CNVs also increase risk for autism spectrum disorders, suggesting an etiologic overlap between these conditions. Recently, de novo duplications of a region on chromosome 7q11.23 were associated with autism spectrum disorders. The reciprocal deletion of this region causes Williams-Beuren syndrome.


We assayed an Ashkenazi Jewish cohort of 554 SZ cases and 1014 controls for genome-wide CNV. An excess of large rare and de novo CNVs were observed, including a 1.4 Mb duplication on chromosome 7q11.23 identified in two unrelated patients. To test whether this 7q11.23 duplication is also associated with SZ, we obtained data for 14,387 SZ cases and 28,139 controls from seven additional studies with high-resolution genome-wide CNV detection. We performed a meta-analysis, correcting for study population of origin, to assess whether the duplication is associated with SZ.


We found duplications at 7q11.23 in 11 of 14,387 SZ cases with only 1 in 28,139 control subjects (unadjusted odds ratio 21.52, 95% confidence interval: 3.13–922.6, p value 5.5 × 10−5; adjusted odds ratio 10.8, 95% confidence interval: 1.46–79.62, p value .007). Of three SZ duplication carriers with detailed retrospective data, all showed social anxiety and language delay premorbid to SZ onset, consistent with both human studies and animal models of the 7q11.23 duplication.


We have identified a new CNV associated with SZ. Reciprocal duplication of the Williams-Beuren syndrome deletion at chromosome 7q11.23 confers an approximately tenfold increase in risk for SZ.
Keyword 7q11.23 duplication syndrome
Psychiatric genetics
Schizophrenia genetics
Williams-Beuren syndrome
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
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