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Genome-wide linkage scan in a large bipolar disorder sample from the National Institute of Mental Health genetics initiative suggests putative loci for bipolar disorder, psychosis, suicide, and panic disorder

Molecular Psychiatry volume 11, pages 252–260 (2006)Cite this article

Abstract

We conducted a 9-cM genome scan in a large bipolar pedigree sample from the National Institute of Mental Health genetics initiative (1060 individuals from 154 multiplex families). We performed parametric and nonparametric analyses using both standard diagnostic models and comorbid conditions thought to identify phenotypic subtypes: psychosis, suicidal behavior, and panic disorder. Our strongest linkage signals (genome-wide significance) were observed on chromosomes 10q25, 10p12, 16q24, 16p13, and 16p12 using standard diagnostic models, and on 6q25 (suicidal behavior), 7q21 (panic disorder) and 16p12 (psychosis) using phenotypic subtypes. Several other regions were suggestive of linkage, including 1p13 (psychosis), 1p21 (psychosis), 1q44, 2q24 (suicidal behavior), 2p25 (psychosis), 4p16 (psychosis, suicidal behavior), 5p15, 6p25 (psychosis), 8p22 (psychosis), 8q24, 10q21, 10q25 (suicidal behavior), 10p11 (psychosis), 13q32 and 19p13 (psychosis). Over half the implicated regions were identified using phenotypic subtypes. Several regions – 1p, 1q, 6q, 8p, 13q and 16p – have been previously reported to be linked to bipolar disorder. Our results suggest that dissection of the disease phenotype can enrich the harvest of linkage signals and expedite the search for susceptibility genes. This is the first large-scale linkage scan of bipolar disorder to analyze simultaneously bipolar disorder, psychosis, suicidal behavior, and panic disorder.

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Acknowledgements

We are grateful to the patients and family members for their cooperation and support. We thank the treatment facilities and other organizations that expedited the recruitment of the study population. This work was supported by NIMH grant MH59602 (to MB) and by funds from the Columbia Genome Center and New York State Office of Mental Health. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is funded through a federal contract from the National Institutes of Health to Johns Hopkins University (contract N01-HG-65403).

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Author notes

  1. T C Gilliam

    Present address: Department of Human Genetics, University of Chicago, Chicago, IL, USA

Authors and Affiliations

  1. Columbia Genome Center, Columbia University, New York, NY, USA

    R Cheng, S H Juo, T C Gilliam & M Baron

  2. Department of Epidemiology, Columbia University, New York, NY, USA

    S H Juo

  3. Graduate Institute of Medical Genetics, Kaohsiung Medical University, Kaohsiung, Taiwan

    S H Juo

  4. Department of Psychiatry, Columbia University, New York, NY, USA

    J E Loth, J Nee, R Blumenthal, L Sharpe, B Lilliston, M Smith, K Trautman, J Endicott & M Baron

  5. Department of Biomedical Informatics, Columbia University, New York, NY, USA

    I Iossifov

  6. Department of Psychiatry, Hadassah-Hebrew University, Jerusalem, Israel

    K Kanyas & B Lerer

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  1. R Cheng
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Correspondence to M Baron.

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Cheng, R., Juo, S., Loth, J. et al. Genome-wide linkage scan in a large bipolar disorder sample from the National Institute of Mental Health genetics initiative suggests putative loci for bipolar disorder, psychosis, suicide, and panic disorder. Mol Psychiatry 11, 252–260 (2006). https://doi.org/10.1038/sj.mp.4001778

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  • DOI: https://doi.org/10.1038/sj.mp.4001778

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