IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-017-02380-9.html
   My bibliography  Save this article

Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes

Author

Listed:
  • Sílvia Bonàs-Guarch

    (Joint BSC-CRG-IRB Research Program in Computational Biology)

  • Marta Guindo-Martínez

    (Joint BSC-CRG-IRB Research Program in Computational Biology)

  • Irene Miguel-Escalada

    (Institut d’Investigacions August Pi i Sunyer (IDIBAPS)
    Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)
    Imperial College London)

  • Niels Grarup

    (University of Copenhagen)

  • David Sebastian

    (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)
    The Barcelona Institute of Science and Technology
    Universitat de Barcelona)

  • Elias Rodriguez-Fos

    (Joint BSC-CRG-IRB Research Program in Computational Biology)

  • Friman Sánchez

    (Joint BSC-CRG-IRB Research Program in Computational Biology
    Barcelona Supercomputing Center (BSC-CNS))

  • Mercè Planas-Fèlix

    (Joint BSC-CRG-IRB Research Program in Computational Biology)

  • Paula Cortes-Sánchez

    (Joint BSC-CRG-IRB Research Program in Computational Biology)

  • Santi González

    (Joint BSC-CRG-IRB Research Program in Computational Biology)

  • Pascal Timshel

    (University of Copenhagen
    Statens Serum Institut)

  • Tune H. Pers

    (University of Copenhagen
    Statens Serum Institut
    Boston Children’s Hospital
    Broad Institute of MIT and Harvard)

  • Claire C. Morgan

    (Imperial College London)

  • Ignasi Moran

    (Imperial College London)

  • Goutham Atla

    (Institut d’Investigacions August Pi i Sunyer (IDIBAPS)
    Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)
    Imperial College London)

  • Juan R. González

    (Centre for Research in Environmental Epidemiology (CREAL)
    CIBER Epidemiología y Salud Pública (CIBERESP)
    Universitat Pompeu Fabra (UPF))

  • Montserrat Puiggros

    (Joint BSC-CRG-IRB Research Program in Computational Biology)

  • Jonathan Martí

    (Barcelona Supercomputing Center (BSC-CNS))

  • Ehm A. Andersson

    (University of Copenhagen)

  • Carlos Díaz

    (Barcelona Supercomputing Center (BSC-CNS))

  • Rosa M. Badia

    (Barcelona Supercomputing Center (BSC-CNS)
    Spanish Council for Scientific Research (CSIC))

  • Miriam Udler

    (Broad Institute of Harvard and MIT
    Massachusetts General Hospital)

  • Aaron Leong

    (Massachusetts General Hospital
    Massachusetts General Hospital)

  • Varindepal Kaur

    (Massachusetts General Hospital)

  • Jason Flannick

    (Broad Institute of Harvard and MIT
    Massachusetts General Hospital
    Harvard Medical School)

  • Torben Jørgensen

    (Capital Region of Denmark
    University of Copenhagen
    University of Aalborg)

  • Allan Linneberg

    (Capital Region of Denmark
    Rigshospitalet, Glostrup
    University of Copenhagen)

  • Marit E. Jørgensen

    (Steno Diabetes Center
    Southern Denmark University)

  • Daniel R. Witte

    (Aarhus University
    Danish Diabetes Academy)

  • Cramer Christensen

    (Lillebaelt Hospital)

  • Ivan Brandslund

    (Lillebaelt Hospital
    University of Southern Denmark)

  • Emil V. Appel

    (University of Copenhagen)

  • Robert A. Scott

    (Cambridge Biomedical Campus)

  • Jian’an Luan

    (Cambridge Biomedical Campus)

  • Claudia Langenberg

    (Cambridge Biomedical Campus)

  • Nicholas J. Wareham

    (Cambridge Biomedical Campus)

  • Oluf Pedersen

    (University of Copenhagen)

  • Antonio Zorzano

    (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)
    The Barcelona Institute of Science and Technology
    Universitat de Barcelona)

  • Jose C Florez

    (Broad Institute of Harvard and MIT
    Massachusetts General Hospital
    Harvard Medical School)

  • Torben Hansen

    (University of Copenhagen
    University of Southern Denmark)

  • Jorge Ferrer

    (Institut d’Investigacions August Pi i Sunyer (IDIBAPS)
    Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)
    Imperial College London)

  • Josep Maria Mercader

    (Joint BSC-CRG-IRB Research Program in Computational Biology
    Broad Institute of Harvard and MIT
    Massachusetts General Hospital)

  • David Torrents

    (Joint BSC-CRG-IRB Research Program in Computational Biology
    Institució Catalana de Recerca i Estudis Avançats (ICREA))

Abstract

The reanalysis of existing GWAS data represents a powerful and cost-effective opportunity to gain insights into the genetics of complex diseases. By reanalyzing publicly available type 2 diabetes (T2D) genome-wide association studies (GWAS) data for 70,127 subjects, we identify seven novel associated regions, five driven by common variants (LYPLAL1, NEUROG3, CAMKK2, ABO, and GIP genes), one by a low-frequency (EHMT2), and one driven by a rare variant in chromosome Xq23, rs146662075, associated with a twofold increased risk for T2D in males. rs146662075 is located within an active enhancer associated with the expression of Angiotensin II Receptor type 2 gene (AGTR2), a modulator of insulin sensitivity, and exhibits allelic specific activity in muscle cells. Beyond providing insights into the genetics and pathophysiology of T2D, these results also underscore the value of reanalyzing publicly available data using novel genetic resources and analytical approaches.

Suggested Citation

  • Sílvia Bonàs-Guarch & Marta Guindo-Martínez & Irene Miguel-Escalada & Niels Grarup & David Sebastian & Elias Rodriguez-Fos & Friman Sánchez & Mercè Planas-Fèlix & Paula Cortes-Sánchez & Santi González, 2018. "Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02380-9
    DOI: 10.1038/s41467-017-02380-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-017-02380-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-017-02380-9?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. Rebecca A. Lee & Maggie Chang & Nicholas Yiv & Ariel Tsay & Sharon Tian & Danielle Li & Coralie Poulard & Michael R. Stallcup & Miles A. Pufall & Jen-Chywan Wang, 2023. "Transcriptional coactivation by EHMT2 restricts glucocorticoid-induced insulin resistance in a study with male mice," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Wei Fu & Shin-Yi Chou & Li-San Wang, 2022. "NIH Grant Expansion, Ancestral Diversity and Scientific Discovery in Genomics Research," NBER Working Papers 30155, National Bureau of Economic Research, Inc.

    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:9:y:2018:i:1:d:10.1038_s41467-017-02380-9. 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.