Genome-wide association analysis of age at onset and psychotic symptoms in bipolar disorder

Authors

  • Pamela Belmonte Mahon Ph.D.,

    1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland
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  • Mehdi Pirooznia Ph.D.,

    1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland
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  • Fernando S. Goes M.D.,

    1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland
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  • Fayaz Seifuddin M.S.,

    1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland
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  • Jo Steele,

    1. Genetic Basis of Mood and Anxiety Disorders, National Institute of Mental Health Intramural Research Program, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland
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  • Phil Hyoun Lee Ph.D.,

    1. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts
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  • Jie Huang M.D.,

    1. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts
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  • Marian L. Hamshere Ph.D.,

    1. Department of Psychological Medicine, School of Medicine, Cardiff University, Cardiff, UK
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  • The Bipolar Genome Study (BiGS) Consortium, The Wellcome Trust Case Control Consortium Bipolar Disorder Group,

  • J. Raymond DePaulo Jr. M.D.,

    1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland
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  • John R. Kelsoe M.D.,

    1. Department of Psychiatry, University of California, San Diego, La Jolla, California
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  • Marcella Rietschel M.D.,

    1. Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August-Universität, Göttingen, Germany
    2. Department of Psychiatry, University of Bonn, Bonn, Germany
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  • Markus Nöthen Ph.D.,

    1. Institute of Human Genetics, University of Bonn, Bonn, Germany
    2. Departmnet of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
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  • Sven Cichon Ph.D.,

    1. Departmnet of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
    2. Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany
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  • Hugh Gurling M.D.,

    1. Department of Mental Health Sciences, University College London, London, UK
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  • Shaun Purcell Ph.D.,

    1. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts
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  • Jordan W. Smoller M.D.,

    1. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts
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  • Nick Craddock FRCPsych, Ph.D.,

    1. Department of Psychological Medicine, School of Medicine, Cardiff University, Cardiff, UK
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  • Thomas G. Schulze M.D.,

    1. Genetic Basis of Mood and Anxiety Disorders, National Institute of Mental Health Intramural Research Program, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland
    2. Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August-Universität, Göttingen, Germany
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  • Francis J. McMahon M.D.,

    1. Genetic Basis of Mood and Anxiety Disorders, National Institute of Mental Health Intramural Research Program, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland
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  • James B. Potash M.D.,

    1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland
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  • Peter P. Zandi Ph.D.

    Corresponding author
    1. Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
    • Associate Professor, Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Hampton House, Room 857, 624 North Broadway, Baltimore, MD 21205.
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Errata

This article is corrected by:

  1. Errata: Erratum to “Genome-wide association analysis of age at onset and psychotic symptoms in bipolar disorder”, American Journal of Medical Genetics Part B: Neuropsychiatric Genetics”, April 1; 156(3):370–378 Volume 156, Issue 6, 749–750, Article first published online: 10 August 2011

  • Please cite this article as follows: Belmonte Mahon P, Pirooznia M, Goes FS, Seifuddin F, Steele J, Lee PH, Huang J, Hamshere M, The Bipolar Genome Study (BiGS) Consortium, The Wellcome Trust Case Control Consortium Bipolar Disorder Group, DePaulo JR Jr, Kelsoe JR, Rietschel M, Nöthen M, Cichon S, Gurling H, Purcell S, Smoller JW, Craddock N, Schulze TG, McMahon FJ, Potash JB, Zandi PP. 2011. Genome-Wide Association analysis of age at onset and psychotic symptoms in bipolar disorder. Am J Med Genet Part B 156:370–378.

  • Pamela Belmonte Mahon and Mehdi Pirooznia contributed equally to this work.

Abstract

Genome-wide association studies (GWAS) have identified several susceptibility loci for bipolar disorder (BP), most notably ANK3. However, most of the inherited risk for BP remains unexplained. One reason for the limited success may be the genetic heterogeneity of BP. Clinical sub-phenotypes of BP may identify more etiologically homogeneous subsets of patients, which can be studied with increased power to detect genetic variation. Here, we report on a mega-analysis of two widely studied sub-phenotypes of BP, age at onset and psychotic symptoms, which are familial and clinically significant. We combined data from three GWAS: NIMH Bipolar Disorder Genetic Association Information Network (GAIN-BP), NIMH Bipolar Disorder Genome Study (BiGS), and a German sample. The combined sample consisted of 2,836 BP cases with information on sub-phenotypes and 2,744 controls. Imputation was performed, resulting in 2.3 million SNPs available for analysis. No SNP reached genome-wide significance for either sub-phenotype. In addition, no SNP reached genome-wide significance in a meta-analysis with an independent replication sample. We had 80% power to detect associations with a common SNP at an OR of 1.6 for psychotic symptoms and a mean difference of 1.8 years in age at onset. Age at onset and psychotic symptoms in BP may be influenced by many genes of smaller effect sizes or other variants not measured well by SNP arrays, such as rare alleles. © 2011 Wiley-Liss, Inc.

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