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GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways

Author

Listed:
  • Elena López-Isac

    (Institute of Parasitology and Biomedicine López-Neyra, IPBLN-CSIC)

  • Marialbert Acosta-Herrera

    (Institute of Parasitology and Biomedicine López-Neyra, IPBLN-CSIC)

  • Martin Kerick

    (Institute of Parasitology and Biomedicine López-Neyra, IPBLN-CSIC)

  • Shervin Assassi

    (The University of Texas Health Science Center–Houston)

  • Ansuman T. Satpathy

    (Stanford University School of Medicine
    Stanford University)

  • Jeffrey Granja

    (Stanford University School of Medicine
    Stanford University)

  • Maxwell R. Mumbach

    (Stanford University School of Medicine
    Stanford University)

  • Lorenzo Beretta

    (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano)

  • Carmen P. Simeón

    (Valle de Hebrón Hospital)

  • Patricia Carreira

    (12 de Octubre University Hospital)

  • Norberto Ortego-Centeno

    (San Cecilio Clinic University Hospital)

  • Ivan Castellvi

    (Santa Creu i Sant Pau University Hospital)

  • Lara Bossini-Castillo

    (Wellcome Trust Sanger Institute)

  • F. David Carmona

    (University of Granada)

  • Gisela Orozco

    (The University of Manchester)

  • Nicolas Hunzelmann

    (University of Cologne)

  • Jörg H. W. Distler

    (University of Erlangen-Nuremberg)

  • Andre Franke

    (Christian-Albrechts-University of Kiel)

  • Claudio Lunardi

    (Università degli Studi di Verona)

  • Gianluca Moroncini

    (Università Politecnica delle Marche and Ospedali Riuniti)

  • Armando Gabrielli

    (Università Politecnica delle Marche and Ospedali Riuniti)

  • Jeska de Vries-Bouwstra

    (Leiden University Medical Center)

  • Cisca Wijmenga

    (University Medical Center Groningen, University of Groningen)

  • Bobby P. C. Koeleman

    (University Medical Center Utrecht)

  • Annika Nordin

    (Karolinska University Hospital, Karolinska Institute)

  • Leonid Padyukov

    (Karolinska University Hospital, Karolinska Institute)

  • Anna-Maria Hoffmann-Vold

    (Oslo University Hospital)

  • Benedicte Lie

    (University of Oslo and Oslo University Hospital)

  • Susanna Proudman

    (Royal Adelaide Hospital and University of Adelaide)

  • Wendy Stevens

    (St. Vincent’s Hospital)

  • Mandana Nikpour

    (The University of Melbourne at St. Vincent’s Hospital)

  • Timothy Vyse

    (King’s College London)

  • Ariane L. Herrick

    (The University of Manchester, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre
    NIHR Manchester Biomedical Research Centre)

  • Jane Worthington

    (The University of Manchester)

  • Christopher P. Denton

    (Royal Free and University College Medical School)

  • Yannick Allanore

    (INSERM U1016, Paris Descartes University)

  • Matthew A. Brown

    (Queensland University of Technology, Translational Research Institute, Princess Alexandra Hospital)

  • Timothy R. D. J. Radstake

    (University Medical Center Utrecht)

  • Carmen Fonseca

    (Royal Free and University College Medical School)

  • Howard Y. Chang

    (Stanford University School of Medicine
    Stanford University)

  • Maureen D. Mayes

    (The University of Texas Health Science Center–Houston)

  • Javier Martin

    (Institute of Parasitology and Biomedicine López-Neyra, IPBLN-CSIC)

Abstract

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.

Suggested Citation

  • Elena López-Isac & Marialbert Acosta-Herrera & Martin Kerick & Shervin Assassi & Ansuman T. Satpathy & Jeffrey Granja & Maxwell R. Mumbach & Lorenzo Beretta & Carmen P. Simeón & Patricia Carreira & No, 2019. "GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12760-y
    DOI: 10.1038/s41467-019-12760-y
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    Cited by:

    1. Thorunn A. Olafsdottir & Gudmar Thorleifsson & Aitzkoa Lopez de Lapuente Portilla & Stefan Jonsson & Lilja Stefansdottir & Abhishek Niroula & Aslaug Jonasdottir & Hannes P. Eggertsson & Gisli H. Halld, 2024. "Sequence variants influencing the regulation of serum IgG subclass levels," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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