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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; Kähler, Anna K; Sullivan, Patrick F; Kirov, George; Warren, Stephen T.
Afiliación
  • Mulle JG; Department of Epidemiology, Rollins School of Public Health, Emory University; Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia. Electronic address: jmulle@emory.edu.
  • Pulver AE; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
  • McGrath JA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine.
  • Wolyniec PS; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine.
  • Dodd AF; Department of Epidemiology, Rollins School of Public Health, Emory University.
  • Cutler DJ; Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia.
  • Sebat J; Beyster Center for Genomics of Psychiatric Diseases; Department of PsychiatryUniversity of California, San Diego, La Jolla, California; Department of Cellular Molecular and Molecular Medicine, University of California, San Diego, La Jolla, California; Institute for Genomic Medicine, University of Ca
  • Malhotra D; Beyster Center for Genomics of Psychiatric Diseases; Department of PsychiatryUniversity of California, San Diego, La Jolla, California.
  • Nestadt G; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine.
  • Conrad DF; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge.
  • Hurles M; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge.
  • Barnes CP; Department of Cell and Developmental Biology, University College London, London, United Kingdom.
  • Ikeda M; Fujita Health University School of Medicine, Toyake, Aichi, Japan.
  • Iwata N; Fujita Health University School of Medicine, Toyake, Aichi, Japan.
  • Levinson DF; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California.
  • Gejman PV; Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem, Evanston; Department of Psychiatry and Behavioral Sciences, University of Chicago, Chicago, Illinois.
  • Sanders AR; Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem, Evanston; Department of Psychiatry and Behavioral Sciences, University of Chicago, Chicago, Illinois.
  • Duan J; Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem, Evanston; Department of Psychiatry and Behavioral Sciences, University of Chicago, Chicago, Illinois.
  • Mitchell AA; Department of Forensic Biology, Office of Chief Medical Examiner of the City of New York.
  • Peter I; Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York.
  • Sklar P; Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts; Division of Psychiatric Genomics, Department of Psychiatry, Mount Sinai S
  • O'Dushlaine CT; Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts.
  • Grozeva D; Department of Psychological Medicine, Cardiff University, Cardiff, United Kingdom.
  • O'Donovan MC; Department of Psychological Medicine, Cardiff University, Cardiff, United Kingdom.
  • Owen MJ; Department of Psychological Medicine, Cardiff University, Cardiff, United Kingdom.
  • Hultman CM; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Kähler AK; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Departments of Genetics and Psychiatry, University of North Carolina, Chapel Hill, North Carolina; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
  • Sullivan PF; Departments of Genetics and Psychiatry, University of North Carolina, Chapel Hill, North Carolina.
  • Kirov G; Department of Psychological Medicine, Cardiff University, Cardiff, United Kingdom.
  • Warren ST; Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia; Departments of Biochemistry and Pediatrics, Emory University School of Medicine, Atlanta, Georgia.
Biol Psychiatry ; 75(5): 371-7, 2014 Mar 01.
Article en En | MEDLINE | ID: mdl-23871472
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esquizofrenia / Cromosomas Humanos Par 7 / Síndrome de Williams / Variaciones en el Número de Copia de ADN Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Biol Psychiatry Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esquizofrenia / Cromosomas Humanos Par 7 / Síndrome de Williams / Variaciones en el Número de Copia de ADN Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Biol Psychiatry Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos