IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms6966.html
   My bibliography  Save this article

Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci

Author

Listed:
  • Regina C. Betz

    (Institute of Human Genetics, University of Bonn)

  • Lynn Petukhova

    (Columbia University
    Columbia University)

  • Stephan Ripke

    (Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard)

  • Hailiang Huang

    (Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard)

  • Androniki Menelaou

    (University Medical Center Utrecht)

  • Silke Redler

    (Institute of Human Genetics, University of Bonn)

  • Tim Becker

    (German Center for Neurodegenerative Diseases
    Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn)

  • Stefanie Heilmann

    (Institute of Human Genetics, University of Bonn
    Life and Brain Center, University Bonn)

  • Tarek Yamany

    (Columbia University)

  • Madeliene Duvic

    (MD Anderson Cancer Center)

  • Maria Hordinsky

    (University of Minnesota)

  • David Norris

    (University of Colorado)

  • Vera H. Price

    (University of California, San Francisco)

  • Julian Mackay-Wiggan

    (Columbia University)

  • Annemieke de Jong

    (Columbia University)

  • Gina M. DeStefano

    (Columbia University)

  • Susanne Moebus

    (Institute of Medical Informatics, Biometry, and Epidemiology, University Duisburg-Essen)

  • Markus Böhm

    (University of Münster)

  • Ulrike Blume-Peytavi

    (Clinical Research Center for Hair and Skin Science, Charité-Universitätsmedizin Berlin)

  • Hans Wolff

    (University of Munich)

  • Gerhard Lutz

    (Dermatological Practice, Hair and Nail)

  • Roland Kruse

    (Dermatological Practice)

  • Li Bian

    (Columbia University)

  • Christopher I. Amos

    (Community and Family Medicine and Genetics, Dartmouth College)

  • Annette Lee

    (The Feinstein Institute for Medical Research)

  • Peter K. Gregersen

    (The Feinstein Institute for Medical Research)

  • Bettina Blaumeiser

    (University of Antwerp)

  • David Altshuler

    (Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard)

  • Raphael Clynes

    (Columbia University
    Columbia University)

  • Paul I. W. de Bakker

    (University Medical Center Utrecht
    University Medical Center Utrecht)

  • Markus M. Nöthen

    (Institute of Human Genetics, University of Bonn
    Life and Brain Center, University Bonn)

  • Mark J. Daly

    (Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard)

  • Angela M. Christiano

    (Columbia University
    Columbia University)

Abstract

Alopecia areata (AA) is a prevalent autoimmune disease with 10 known susceptibility loci. Here we perform the first meta-analysis of research on AA by combining data from two genome-wide association studies (GWAS), and replication with supplemented ImmunoChip data for a total of 3,253 cases and 7,543 controls. The strongest region of association is the major histocompatibility complex, where we fine-map four independent effects, all implicating human leukocyte antigen-DR as a key aetiologic driver. Outside the major histocompatibility complex, we identify two novel loci that exceed the threshold of statistical significance, containing ACOXL/BCL2L11(BIM) (2q13); GARP (LRRC32) (11q13.5), as well as a third nominally significant region SH2B3(LNK)/ATXN2 (12q24.12). Candidate susceptibility gene expression analysis in these regions demonstrates expression in relevant immune cells and the hair follicle. We integrate our results with data from seven other autoimmune diseases and provide insight into the alignment of AA within these disorders. Our findings uncover new molecular pathways disrupted in AA, including autophagy/apoptosis, transforming growth factor beta/Tregs and JAK kinase signalling, and support the causal role of aberrant immune processes in AA.

Suggested Citation

  • Regina C. Betz & Lynn Petukhova & Stephan Ripke & Hailiang Huang & Androniki Menelaou & Silke Redler & Tim Becker & Stefanie Heilmann & Tarek Yamany & Madeliene Duvic & Maria Hordinsky & David Norris , 2015. "Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci," Nature Communications, Nature, vol. 6(1), pages 1-8, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms6966
    DOI: 10.1038/ncomms6966
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms6966
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms6966?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. Junyan Duan & Michelle N. Ngo & Satya Swaroop Karri & Lam C. Tsoi & Johann E. Gudjonsson & Babak Shahbaba & John Lowengrub & Bogi Andersen, 2024. "tauFisher predicts circadian time from a single sample of bulk and single-cell pseudobulk transcriptomic data," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Stephanie O. Erjavec & Sahar Gelfman & Alexa R. Abdelaziz & Eunice Y. Lee & Isha Monga & Anna Alkelai & Iuliana Ionita-Laza & Lynn Petukhova & Angela M. Christiano, 2022. "Whole exome sequencing in Alopecia Areata identifies rare variants in KRT82," Nature Communications, Nature, vol. 13(1), pages 1-13, 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:6:y:2015:i:1:d:10.1038_ncomms6966. 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.