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Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder.
Charney, A W; Ruderfer, D M; Stahl, E A; Moran, J L; Chambert, K; Belliveau, R A; Forty, L; Gordon-Smith, K; Di Florio, A; Lee, P H; Bromet, E J; Buckley, P F; Escamilla, M A; Fanous, A H; Fochtmann, L J; Lehrer, D S; Malaspina, D; Marder, S R; Morley, C P; Nicolini, H; Perkins, D O; Rakofsky, J J; Rapaport, M H; Medeiros, H; Sobell, J L; Green, E K; Backlund, L; Bergen, S E; Juréus, A; Schalling, M; Lichtenstein, P; Roussos, P; Knowles, J A; Jones, I; Jones, L A; Hultman, C M; Perlis, R H; Purcell, S M; McCarroll, S A; Pato, C N; Pato, M T; Craddock, N; Landén, M; Smoller, J W; Sklar, P.
Afiliación
  • Charney AW; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, USA.
  • Ruderfer DM; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, USA.
  • Stahl EA; Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, USA.
  • Moran JL; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, USA.
  • Chambert K; Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, USA.
  • Belliveau RA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Forty L; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Gordon-Smith K; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Di Florio A; MRC Centre for Psychiatric Genetics and Genomics, Cardiff Unviersity, Cardiff, UK.
  • Lee PH; Department of Psychological Medicine, University of Worcester, Worcester, UK.
  • Bromet EJ; MRC Centre for Psychiatric Genetics and Genomics, Cardiff Unviersity, Cardiff, UK.
  • Buckley PF; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Escamilla MA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Fanous AH; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
  • Fochtmann LJ; Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
  • Lehrer DS; Department of Psychiatry, Stony Brook University, Stony Brook, NY, USA.
  • Malaspina D; Department of Psychiatry, Georgia Regents University Medical Center, Augusta, GA, USA.
  • Marder SR; Center of Excellence in Neuroscience, Department of Psychiatry, Texas Tech University Health Sciences Center at El Paso, El Paso, TX, USA.
  • Morley CP; Department of Psychiatry, Veterans Administration Medical Center, Washington, DC, USA.
  • Nicolini H; Department of Psychiatry, Georgetown University, Washington, DC, USA.
  • Perkins DO; Department of Psychiatry, Stony Brook University, Stony Brook, NY, USA.
  • Rakofsky JJ; Department of Psychiatry, Wright State University, Dayton, OH, USA.
  • Rapaport MH; Department of Psychiatry, New York University, New York, NY, USA.
  • Medeiros H; Department of Psychiatry, University of California, Los Angeles, Los Angeles, CA, USA.
  • Sobell JL; Department of Psychiatry and Behavioral Science, State University of New York, Upstate Medical University, Syracuse, NY, USA.
  • Green EK; Departments of Family Medicine, State University of New York, Upstate Medical University, Syracuse, NY, USA.
  • Backlund L; Department of Public Health and Preventive Medicine, State University of New York, Upstate Medical University, Syracuse, NY, USA.
  • Bergen SE; Center for Genomic Sciences, Universidad Autónoma de la Ciudad de México, Mexico City, Mexico.
  • Juréus A; Department of Psychiatry, Carracci Medical Group, Mexico City, Mexico.
  • Schalling M; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Lichtenstein P; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.
  • Roussos P; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.
  • Knowles JA; Department of Psychiatry and the Behavioral Sciences, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA.
  • Jones I; Department of Psychiatry and the Behavioral Sciences, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA.
  • Jones LA; School of Biomedical and Health Sciences, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth University, Plymouth, UK.
  • Hultman CM; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • Perlis RH; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • Purcell SM; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • McCarroll SA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Pato CN; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Pato MT; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • Craddock N; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Landén M; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, USA.
  • Smoller JW; Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, USA.
  • Sklar P; Friedman Brain Institute, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, USA.
Transl Psychiatry ; 7(1): e993, 2017 01 10.
Article en En | MEDLINE | ID: mdl-28072414
We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10-8) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h2=0.35; BD II SNP-h2=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastornos Psicóticos / Trastorno Bipolar Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Transl Psychiatry Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastornos Psicóticos / Trastorno Bipolar Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Transl Psychiatry Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos