IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v4y2013i1d10.1038_ncomms3739.html
   My bibliography  Save this article

Genome-wide association study implicates NDST3 in schizophrenia and bipolar disorder

Author

Listed:
  • Todd Lencz

    (Division of Research, Department of Psychiatry, The Zucker Hillside Hospital Division of the North Shore—Long Island Jewish Health System
    Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research
    Albert Einstein College of Medicine of Yeshiva University
    Hofstra University School of Medicine)

  • Saurav Guha

    (Division of Research, Department of Psychiatry, The Zucker Hillside Hospital Division of the North Shore—Long Island Jewish Health System)

  • Chunyu Liu

    (University of Illinois at Chicago)

  • Jeffrey Rosenfeld

    (Division of Research, Department of Psychiatry, The Zucker Hillside Hospital Division of the North Shore—Long Island Jewish Health System)

  • Semanti Mukherjee

    (Division of Research, Department of Psychiatry, The Zucker Hillside Hospital Division of the North Shore—Long Island Jewish Health System)

  • Pamela DeRosse

    (Division of Research, Department of Psychiatry, The Zucker Hillside Hospital Division of the North Shore—Long Island Jewish Health System)

  • Majnu John

    (Division of Research, Department of Psychiatry, The Zucker Hillside Hospital Division of the North Shore—Long Island Jewish Health System)

  • Lijun Cheng

    (University of Chicago)

  • Chunling Zhang

    (University of Chicago)

  • Judith A. Badner

    (University of Chicago)

  • Masashi Ikeda

    (School of Medicine, Fujita Health University)

  • Nakao Iwata

    (School of Medicine, Fujita Health University)

  • Sven Cichon

    (Institute of Human Genetics, University of Bonn)

  • Marcella Rietschel

    (Central Institute of Mental Health, University of Mannheim)

  • Markus M. Nöthen

    (Institute of Human Genetics, University of Bonn)

  • A.T.A. Cheng

    (Institute of Biomedical Sciences, Academia Sinica)

  • Colin Hodgkinson

    (Laboratory of Neurogenetics, NIAAA)

  • Qiaoping Yuan

    (Laboratory of Neurogenetics, NIAAA)

  • John M. Kane

    (Division of Research, Department of Psychiatry, The Zucker Hillside Hospital Division of the North Shore—Long Island Jewish Health System
    Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research
    Albert Einstein College of Medicine of Yeshiva University
    Hofstra University School of Medicine)

  • Annette T. Lee

    (Robert S. Boas Center for Human Genetics and Genomics, The Feinstein Institute for Medical Research)

  • Anne Pisanté

    (The Institute of Life Sciences, The Hebrew University of Jerusalem)

  • Peter K. Gregersen

    (Robert S. Boas Center for Human Genetics and Genomics, The Feinstein Institute for Medical Research
    Hofstra University School of Medicine)

  • Itsik Pe’er

    (Columbia University)

  • Anil K. Malhotra

    (Division of Research, Department of Psychiatry, The Zucker Hillside Hospital Division of the North Shore—Long Island Jewish Health System
    Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research
    Albert Einstein College of Medicine of Yeshiva University
    Hofstra University School of Medicine)

  • David Goldman

    (Laboratory of Neurogenetics, NIAAA)

  • Ariel Darvasi

    (The Institute of Life Sciences, The Hebrew University of Jerusalem)

Abstract

Schizophrenia and bipolar disorder are major psychiatric disorders with high heritability and overlapping genetic variance. Here we perform a genome-wide association study in an ethnically homogeneous cohort of 904 schizophrenia cases and 1,640 controls drawn from the Ashkenazi Jewish population. We identify a novel genome-wide significant risk locus at chromosome 4q26, demonstrating the potential advantages of this founder population for gene discovery. The top single-nucleotide polymorphism (SNP; rs11098403) demonstrates consistent effects across 11 replication and extension cohorts, totalling 23, 191 samples across multiple ethnicities, regardless of diagnosis (schizophrenia or bipolar disorder), resulting in Pmeta=9.49 × 10−12 (odds ratio (OR)=1.13, 95% confidence interval (CI): 1.08–1.17) across both disorders and Pmeta=2.67 × 10−8 (OR=1.15, 95% CI: 1.08–1.21) for schizophrenia alone. In addition, this intergenic SNP significantly predicts postmortem cerebellar gene expression of NDST3, which encodes an enzyme critical to heparan sulphate metabolism. Heparan sulphate binding is critical to neurite outgrowth, axon formation and synaptic processes thought to be aberrant in these disorders.

Suggested Citation

  • Todd Lencz & Saurav Guha & Chunyu Liu & Jeffrey Rosenfeld & Semanti Mukherjee & Pamela DeRosse & Majnu John & Lijun Cheng & Chunling Zhang & Judith A. Badner & Masashi Ikeda & Nakao Iwata & Sven Cicho, 2013. "Genome-wide association study implicates NDST3 in schizophrenia and bipolar disorder," Nature Communications, Nature, vol. 4(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3739
    DOI: 10.1038/ncomms3739
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms3739
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms3739?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Courtney J. Mycroft-West & Sahar Abdelkarim & Helen M. E. Duyvesteyn & Neha S. Gandhi & Mark A. Skidmore & Raymond J. Owens & Liang Wu, 2024. "Structural and mechanistic characterization of bifunctional heparan sulfate N-deacetylase-N-sulfotransferase 1," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3739. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.